Download Cell Quiz Review

Hematology PPT Flashcards Unit 3
Factors that regulate the commitment of human
hematopoietic progenitor cell to a specific cell
line are influenced by what?
What are the growth of these cells dependent
on?
The microenvironment of the progenitor cell
favors differential development of what two
cell series?
In addition to the differentiation of
granulocytes and monocytes, what also
stimulates specific differentiation such as the
development of eosinophils?
The development, distribution, and
destruction of neutrophils, eosinophils, and
basophils are collectively referred to as
what?
What location in the body do neutrophils,
basophils, and eosinophils begin as
multipotential cells?
What location in the body do these cells
continue through the processes of
differentiation, multiplication and maturation?
After developing into either band or segmented
forms, mature cells enter into what location in
the body?
What is the first identifiable cell in the
granulocytic series?
Myeloblast make up what percentage of the
total nucleated bone marrow cells?
How long does this stage last?
What cell in this this bone barrow stage lasts
about 24 hours and is approximately 3% of the
nucleated bone marrow cells?
This cell is approximately 12% of the
proliferative cells existing in the bones marrow
stage.
The stage from myelocyte to _______ last an
average of 4.3 days. Once this stage has been
reached, cells have undergone four or five cell
divisions. The proliferative ends.
Once the cell line becomes committed to
developing in to a myeloblast, the maturational
development from the myeloblast through the
myelocyte stage and the mitotic division take
place in what is referred to as the bone
marrow’s ______ ______. This is also called
1)
2)
3)
1)
2)
1)
2)
Hematopoietic growth factors
Interleukins
microenvironment
Colony stimulating factor (CSF)
Interleukins
Granulocytic (myeloid) series
Macrophage-monocytic series
Colony Stimulating Factor
Granulocytic kinetics
Bone marrow
Bone marrow
Blood circulation
Myeloblast
One percent
Approximately 15 hours
Promyelocyte
Myelocyte
Meatamyelocyte
proliferative compartment
1
Hematology PPT Flashcards Unit 3
the mitotic pool and includes cells callable of
DNA synthesis.
Following the proliferative stage, granulocytes
enter a ____-_____ compartment .
The metamyelocytes and band forms mature
into segmented granulocytes in this
compartment of the bone marrow. The relative
proportions of the cells are approximately
45%______, 34%_____, and 20%______,
respectively.
Segmented neutrophils in the maturation-storage
compartment are frequently referred to as the ___
___.
This constitutes a 4 to 8 day supply of
neutrophils.
It is estimated that neutrophilic granulocytes
normally remain in the maturation-storage phase
for 7 to _ days.
Eosinophils remain for about 2.5 days. And
basophils remain in this phase for the shortest
period of approximately __ hours.
Certain characteristics and physiological regulators
promote movement of the granulocytes through
the ____ wall of the bone marrow, which, is
normally an anatomical barrier.
As cells mature, they are able to move through the
sinusoid of the bone marrow because of a ___
oversize cell size, a ___ nuclear cytoplasmic ratio,
and ____ flexibility and mobility.
The peripheral blood circulation is subsequently
divided into two pools of equal size. A ___ pool
and a ___ pool.
The marginating granulocytes adhere to the ___ of
the blood vessels.
Mature granulocytes in the peripheral blood are
only in transit to their potential sites of action in
the ___.
The process were movement of granulocytes
from the circulation pool to the peripheral
occur is called?
The average life span of segmented neutrophilic
granulocyte in the circulating blood is about 7 to
10 hours. Once mature cells have migrated in to
the tissues, their life spanis considered to be
several days unless the cells encounter ___, ___, or
___.
maturation-storage compartment
45%Metamyelocytes
35% Band from neutrophils
20% Segmented neutrophils
marrow reserve
7 to 10 days
12 hours
sinusoid wall
decreased
decreased
increased
circulating pool
marginating pool
endothelium
tissue
Diapedesis
antigens, toxins, or microorganisms
2
Hematology PPT Flashcards Unit 3
Eosinophils are in the peripheral blood for a few
hours and are believed to reside in the ____ for
several days.
Basophils have an average circulating time of
about 8.5 hours. If excessive numbers of
eosinophils are preens because of a disease state,
damage or degenerated eosinophils give rise to
____-____ ____ found in the body secretions such
as the sputum and stool.
If cells are not prematurely destroyed while
defending the body, they sew sloughed off with
various body secretions, such as the ___, ____, or
______ secretions.
Two stages of granulocytes are observed ion the
circulating blood. _____ form and ______
(polymorphonuclear) form.
Both the band form of neutrophils, eosinophils,
and basophils and, in the final stage of maturation,
the segmented neutrophils, and basophils are the
cell forms normally found in the ___ ___.
Which mature form of granulocyte typically has an
elongated nucleus?
Which mature form of granulocyte has a
characteristic multilobed nucleus?
What are the antibacterial substances rich within
the granules of segmented neutrophils?
How do Eosinophilic granules differ from
Neutrophilic granules?
What are the two types of Eosinophilic granules?
Which type of Eosinophilic granule does not
contain crystalloids?
What are the characteristics of small round
granules of mature Eosinophils?
Which type of Eosinophilic granule is more
numerous?
Which type of Eosinophilic granule has an
elliptical shape and is larger than neutrophilic
granules?
Which type of Eosinophilic granule has an
amorphous matrix surrounding an internal
crystalline structure?
What type of granulocyte has granules that contain
both heparin and histamine?
Which type of granulocyte has granules that have
an enzyme content similar to those of blood
tissue
Charcot-Leyden crystals
urine
saliva
gastroinestinal secretions
Band form
segmented (polymorphonuclear) form
circulating blood
Band form
Segemented Neutrophil
Lysosomal hydrolases, Lysozyme,
Myeloperoxidase
Neutrophilic granules contain Lysozymes
Small round granules and large crystalline
granules
Small round granules
Exist in small quantities and are rich in
acid phosphtase
Large crystalloid granules
Large crystalloid granules
Large Crystalline granules
Basophil
Mast cells
3
Hematology PPT Flashcards Unit 3
basophil?
What are the two cell types included in the
mononuclear phagocyte system?
What is the name of a macrophage in the loose
connective tissues?
What is the name of a macrophage in the sinusoids
of the liver?
What is the name of a macrophage in the bone?
What is the name of a macrophage in the nervous
system?
What type of cell changes its name depending on
its location within the body?
Which cells, along with the reticular cells of the
spleen, thymus, and lymphoid tissues, are
collectively referred to as the mononuclear
phagocyte system?
Which phagocytic cell is confined to the
circulation blood unless recruited in the tissues?
Which type of cells is formed from the progenitor
cells in the bone marrow?
Which cells are derived from the CFU-GM?
Which cell type is influenced by hematopoietic
growth factors and transforms into a macrophage
in the tissues?
What is the major role of monocytes and
macrophages?
________ are released into the circulating blood
within 12 to 24 hours after their precursors have
completed their last mitotic division.
Granulocytes and _______ have no large reserve
of cells in a maturation-storage pool.
Once the monocytes have entered the circulation,
cells may be located in a _______ or ________
pool.
The ratio of monocytic circulating and marginating
cells is ______.
What is the circulatory half-life of a Monocyte?
Monocytic cells in noninflammatory tissue areas
have been demonstrated to live for?
What is the main function of granulocytic
leukocytes?
A macrophage can exist as either a _____ or
________ cells.
Macrophages are important in the processing of
_______ as a part of the immune response.
______ is an infection-induced syndrome defined
Monocytes and Macrophages
Histiocytes
Kupffer cells
Osteoclasts
Microglial cells
Macrophage
Monocytes and Macrophages
Segmented neutrophil
Macrophages
Macrophages
Monocyte
Phagocytosis
Monocytes
Monocytes
Circulating/ Marginating
1:3.5
8.5 hours
Months to years
Phagocytosis
Fixed/ wandering
Antigens
Sepsis
4
Hematology PPT Flashcards Unit 3
as the presence of two or more features of systemic
inflammation.
With the presence of two or more of these features, Fever, hypothermia, Leukocytosis,
a patient may be experiencing Sepsis.
leuopenia, tachycardia, tachypnea and
supranormal minute ventilation
What are the three stages of Phagocytosis?
Movement of cells, Engulfment, Digestion
Which granulocyte attempts to suppress
Eosinophils
inflammatory tissue reactions to prevent the
excessive spread of inflammation?
What is the primary function of Eosinophils?
To react with products from mast cells,
lymphocytes and other soluble substances
in the blood.
Eosinophils regulate what types of diseases?
Allergic
What is the name of a Basophil that is in the
Mast cell
tissues?
Basophils possess metachromatic granules
Immunoglobulin E (IgE)
containing histamine, and proteoglycans and
express a high-affinity for which immunoglobulin
receptor?
What plays an important role in acute, systemic
Histamine
allergic reactions?
In addition to phagocytosis, monocytes are able to Transferring, complement, interferon, and
synthesize various biologically important
certain growth factors
compounds such as:
In cellular immunity, monocytes assume what
The killer role
role?
In the killer role, Monocytes are activated by
Phagocytize
sensitized lymphocytes in order to _______
offending cells or antigen particles.
Name the six assessment methods
Total leukocyte count
Differential blood smear evaluation
Absolute cell counts
Erythrocyte sedimentation rate
Assessment of eosinophils and basophils
Leukocyte alkaline phosphatase test
Which test assesses the killing ability of
Nitroblue tetrazolium test (NBT)
granulocytes?
How many lobes does a mature segemented
2-5 lobes
neutrophil have?
Counting the number of lobes in a mature
Hypersegmentation index (NHI)
segmented neutrophil can be performed to
determine the ______________?
Conditions such as Sepsis and chronic nephritis
Right
will create a shift in what direction?
The NHI is clinically useful in the diagnosis
B12 and folic acid deficiency
of_________
5
Hematology PPT Flashcards Unit 3
What are the three types of ways to calculate
Neutrophilic Hypersegmentation Index?
This method of NHI calculations is determined
counting the number of lobes in a number of
neutrophils and dividing by the total number of
neutrophils
This method of NHI calculations is done by
counting the number of lobes in randomly selected
segmented neutrophils. Add up the total number of
lobes for each segmented neutrophils counted and
divide by the total number of cells counted.
This method of NHI calculations uses a minimum
of 200 segmented cells.
An NHI value greater than 16.9 indicates
_________?
What kind of disorder of granulocytes range from
general increases or decreases in the total
leukocyte count?
What is an example of a qualitative disorder of
granulocytes
True or False?
A variety of laboratory tests can be used to asses
disorders related to granulocytes and monocytes.
True or False?
Leukocytosis is defined as a decrease in the
concentration of percentage of any of the
leukocytes in the peripheral blood: neutrophils,
eosinophils, basophils, monocytes, or
lymphocytes.
What is defined as a decrease in the total leukocyte
count?
Nonmalignant leukocytosis can be caused by:
(Increase or Decrease)
A. ________ movement of immature cells out of
the bone marrow’s proliferative compartment
B. ________ mobilization of cells from the
maturation-storage compartment of the bone
marrow to the peripheral blood
C. ________ movement of mature cells from the
marginating pool to the circulating pool
D. ________ movement of mature cells from the
circulation into the tissues
True or False?
Lobe average
Percentage of neutrophils with five or more
lobes
Hypersegmentation index
Lobe Average
Percentage of neutrophils with five or more
lobes
Hypersegmentation index
Hypersegmentation
Nonmalignant disorders of granulocytes
A defect of the killing ability of leukocytes
True
False. Leukocytosis is an increase in the
concentration or percentage of any of the
leukocytes in the peripheral blood:
neutrophils, eosinophils, basophils,
monocytes, or lymphocytes.
Leukocytopenia
A. Increased
B. Increased
C. Increased
D. Decreased
False. They are quantitative disorders
6
Hematology PPT Flashcards Unit 3
Neutrophilia and Eosinophilia are qualitative
disorders.
What is an increase in number or neutrophils?
True or False?
Neutrophilia can be present in some forms of
leukemia and nonmalignant conditions (such as
inflammatory conditions or infection)
Name 7 physical stimuli that can cause
neutrophilia
True or False?
Some drugs and hormones can not produce
neutrophilia
Define eosinophilia
When can eosinophilia be observed?
What can be found in the tissues, exudates,
sputum, and stool of patients with active
eosinophilic inflammation?
Define basophilia
True or False?
The number of circulating basophils is not affected
by factors such as time of day, age, and physical
activity
What can cause an increase in basophils?
What kinds of disorders can basophilia be seen in?
What is known as an increase in the number of
monocytes in the blood?
Why is the association of monocytosis with
disease not entirely accurate?
Define Leukocytopenia
Neutrophilia
True
Heat, cold, surgery, burns, vigorous
exercise, nausea, and vomiting
False. Some drugs and hormones may
produce neutrophilia
Increased numbers of eosinophils
In active allergic disorders such as asthma
and hay fever
Chorcot-Leyden crystals
An abnormal increase in the number of
basophils
True
Hormones can cause in increase in
basophils
Ulcerative colitis and chronic sinusitis
Monocytosis
Because the normal value of circulating
monocytes is not precisely defined
A reduction in the number of leukocytes in
the blood
The segmented neutrophil
What is the major leukocyte type associated with
leukocytopenia or granulocytopenia?
How can abnormalities of mature granulocytes be
Through stained smears of peripheral blood
observed?
What is defined as a condition in which prominent Toxic granulation
dark granulation (fine or heavy) can be observed in
band and segmented neutrophils or monocytes
7
Hematology PPT Flashcards Unit 3
What is toxic granulation frequently associated
with?
What kinds of conditions can toxic granulation be
seen in?
What is defined as inclusion bodies as single or
multiple (light-blue staining inclusions) on Writestained blood smears?
Where are Dohle Bodies usually seen?
Where are Dohle Bodies predominantly seen?
Dohle Bodies may be seen in _______ or
________.
What do Dohle bodies represent?
What kinds of conditions may be associated with
Dohle Bodies?
What is most frequently seen in segmented
neutrophils with more than five lobes or nuclear
segments?
Infectious states
Burns, malignant disorders, or the result of
drug therapy
Dohle Bodies
Near the periphery of the cytoplasm
In neutrophils
Monocytes or lymphocytes
Aggregates of rough endoplasmic
reticulum
Viral infections, burns, certain drugs, and
May-Hegglin anomaly
Hypersegmentation
Deficiencies of _________ or _________ is
associated with hypersegmentation
Hypersegmentation can exist along with what
other conditions?
Pseudohypersegmentation can be seen in (old/new)
segmented neutrophils
Define Pelger-Huet anomaly
Vitamin B12 or folic acid
What is a reflection of abnormal nucleic acid
metabolism?
Despite the abnormal morphology of the described
condition above, is the cell still functional?
Abnormal nuclear maturation
Abnormal enlarged oval-shaped
erythrocyte
Old
Hyposegmentation of mature neutrophils
Yes.
8
Hematology PPT Flashcards Unit 3
Abnormal nuclear maturation is considered to be a
_________ anomaly
Pseudoanomaly may be caused by? (2 causes)
How can May-Hegglin anomaly can be
characterized?
Benign
1. drug induced
maturational arrest associated with acute
infections
By the presence of Dohle body-like
inclusions in neutrophils, eosinophils, and
monocytes
What kind of conditions co-exist in May-Hegglin
anomaly?
What is the percentage of patients who do not have
symptoms of May-Hegglin Anomaly?
Those who do show symptoms usually
have______________
What is defined as a rare morphological
abnormality of mature granulocytes that is
considered a hereditary disease?
How is Chediak-Higashi syndrome characterized?
Abnormally large and poor granulated
platelets, and thrombocytopenia
50%
In Chediak-Higashi Syndrome, which WBC
displays impaired chemotaxis and a delayed killing
of ingested bacteria?
Patients with Chediak-Higashi Syndrome suffer
from frequent infections, which signify what?
Alder-Reilly inclusions indicate what color
particles?
Neutrophils
What are these particles? And which cells are they
mainly seen in?
These particles are sometimes seen in which cells?
Alder-Reilly granules resemble __________
Mucopolysaccharides seen mainly in
neutrophils, eosinophils, basophils.
Monocytes and lymphocytes
Toxic granulation
Abnormal bleeding tendencies
Chediak-Higashi syndrome
Very large granules that represend
abnormal lysosomal development in
neutrophils and other leukocytes
That neutrophils are not efficient
bacteriocidal cells
Purple-red
9
Hematology PPT Flashcards Unit 3
____________.
Alder-Reilly granules are mostly seen in what kind
of patients?
True or False: Is Ehrlichia a morphological
abnormality of mature granulocytes?
What is the correct technical name of Ehrlichia?
When was ehrlichial infection of humans in the
United States and was first described in?
True or False: Does Ehlrichia represents the
second most recognized human infection in the
United States?
Give 2 examples of abnormal inclusions can be
seen in granulocytes obtained from body fluids.
Name 3 types of Qualitative Disorders.
What is defective locomotion and chemotaxis?
Defective locomotion and chemotaxis is
commonly seen in patients who have __?
Define defects in microbicidal activity?
Defects in microbicidal activity disorders include
___?
Name 2 defects in microbicidal activity.
How many hereditary defects and additional
disorders of neutrophil function have been
described.
True or False: Lactoferrin deficiency is a
functional anomaly of neutrophils?
Give 2 examples of Monocyte-macrophage
disorders.
What is Gaucher disease is caused by?
What is Neimann-Pick?
Patients with Hurler, Hunter, and
Maroteaux-Lamy types of genetic
mucopolysaccharidosis.
True
Human granulocytic ehrlichiosis (HGE)
represents the second recognized.
1994
True
1. Bacteria
Histoplasma capsulatum
1. Defective locomotion and chemotaxis
2. Defects in microbicidal activity
• Monocyte-macrophage disorders
- A significant defect in the cellular
response to chemotaxis
 Diabetes mellitus
Chédiak-Higashi anomaly
 Sepsis
- High levels of antibody IgE, (Job
syndrome)
• Neutrophils and monocytes possess
oxidase systems capable of killing
ingested microorganisms in the process
of phagocytosis.
 CGD
 Myeloperoxidase deficiency
• Other functional anomalies of
neutrophils.
1. Chronic granulomatous disease
2. Myeloperoxidase deficiency
•
• 15 and 30
•
True
1. Gaucher disease
• Niemann-Pick disease
• A disturbance in cellular lipid
metabolism.
• An inherited abnormality of lipid
10
Hematology PPT Flashcards Unit 3
What do Human granulocytic ehrlichiosis (HGE)
represent?
Where can certain abnormalities of mature
granulocytes be found?
What are three qualitative disorders?
A significant defect in the cellular response to
chemotaxis is seen in what kinds of patients?
Disorders due to defects in microbicide activity?
How many disorders of neutrophil function have
been described?
A functional anomaly of neutrophils includes
what?
What are two monocyte-macrophage disorders?
What is Gaucher disease is caused by?
What is Niemann-Pick Disease?
The lymphocytes and plasma cells cooperate in
defending the body against, what?
How does the lymphocytes and plasma cells
defending the body against disease?
During embryonic development, Where does
lymphocytes arise from the pluripotent, precursor
cells?
Later in fetal development and throughout the life
cycle, Where is the sole provider of hematopoietic
stem cells?
Name the 2 Primary lymphoid tissues.
Name the 3 locations of Secondary lymphoid
tissues.
What does proliferation of the T and B
lymphocytes in the secondary or peripheral
lymphoid tissues is primarily depend on?
Name the following 4 regions The T lymphocytes
or T cells are located in:
metabolism. Sphingomyelin
accumulates in the tissue macrophages
the second recognized ehrlichial infection
of humans in the United States and was
first described in 1994
Certain abnormal inclusions can be seen in
granulocytes obtained from body fluids
Defective locomotion and chemotaxis,
microbicidal activity, monocytemacrophage disorders
diabetes mellitus, Chédiak-Higashi
anomaly, and sepsis as well as in patients
with high levels of antibody IgE, such as
those with Job syndrome
These disorders include CGD,
myeloperoxidase deficiency, and other
functional anomalies of neutrophils.
At least 15 hereditary defects and 30
disorders
includes lactoferrin deficiency.
Gaucher disease, Niemann-Pick disease
a disturbance in cellular lipid metabolism
an inherited abnormality of lipid
metabolism. Sphingomyelin accumulates in
the tissue macrophages.
Diseases
Through recognition of foreign antigens
and antibody production.
Yolk sac and Liver
Bone marrow
1. Bone marrow
Thymus
1. Lymph nodes
2. Spleen
• Peyer patches in the intestine
2. Antigenic stimulation
1. Perifollicular and paracortical regions
of the lymph node
11
Hematology PPT Flashcards Unit 3
What are the 4 site B lymphocytes, or B cells,
multiply and populate?
2.
3.
3.
1.
2.
3.
What is the lifespan of a mature T lymphocyte?
What is the average life span of the B
lymphocytes?
What are the stages of lymphocyte development?
How are general variations in lymphocyte
morphology?
What are general characteristics of variant
lymphocytes?
How many specific lymphocytes morphological
vitiate?
What are binucleated lymphocytes?
2.
3.
4.
Medullary cords of the lymph nodes
Periarteriolar regions of the spleen
Thoracic duct of the circulatory system
Follicular and medullary areas
(germinal centers) of the lymph nodes
Primary follicles and red pulp of the
spleen
Follicular regions of gut-associated
lymphoid tissue (GALT)
Medullary cords of the lymph nodes
Several months or years
Few Days
These are: lymphoblast, prolymphocyte,
and mature lymphocyte.
The term variant denotes that a lymphocyte
is not normal but does not further classify a
lymphocyte.
Healthy persons may have up to 5% or 6%
of variant lymphocytes.
Usually, the overall size is increased (16 to
30 mm).
The nucleus may be enlarged.
The nuclear shape may be lobulated or
resemble the nucleus of a monocyte
(monocytoid) with clefts or notching and
may be folded.
Chromatin patterns vary from fine patterns
to a coarsely granular appearance.
One to three nucleoli may be present.
The cytoplasm is frequently abundant and
often foamy or vacuolated.
Cytoplasmic color may range from gray to
light blue or intensely blue.
Granules may be present
Binucleated lymphocytes
Rieder cells
Vacuolated lymphocytes
Smudge cells
Binucleated lymphocytes are seen in viral
infections. If more than 5% of the
lymphocytes are binucleated, it suggestive
of either lymphocytic leukemia or
leukosarcoma.
12
Hematology PPT Flashcards Unit 3
What is rieder cell?
What are smudge cells?
How smudge cell represent?
What are vacuolated lymphocytes?
How many major lymphocyte categories and
functions are recognized?
What are T cells responsible for?
How is about B lymphocyte responsed?
How natural killer lymphocytes are recognized?
Rieder cells are similar to normal
lymphocytes, except that the nucleus is
notched, lobulated, and cloverleaf-like.
They occur in chronic lymphocytic
leukemia or can be artificially produced
through blood smear preparation.
Smudge cell is a natural artifact produced
in the preparation of a blood smear.
Increased fragility of cells contributes to
the increased percentage of smudge cells.
Some laboratories enumerate smudge cells
as a percentage of the total 100 leukocytes
in a differential leukocyte count.
Smudge cells are seen in increased
proportions in lymphocytosis, particularly
chronic lymphocytic leukemia.
They are frequently associated with
Niemann-Pick disease, Tay-Sachs disease,
Hurler syndrome, and Burkitt lymphoma.
Vacuoles can also be seen in variant
lymphocytes and as a reaction to viral
infections, radiation, and chemotherapy
These categories are: T cells, B cells, and
natural killer (NK) lymphocytes.
T cells are responsible for cellular immune
responses and are involved in the
regulation of antibody reactions by either
helping or suppressing the activation of B
lymphocyte.
Sensitized T lymphocytes protect humans
against infection by mediating intracellular
pathogens that are viral, bacterial, fungal,
or protozoan.
These cells are responsible for chronic
rejection in organ transplantation
B cells serve as the primary source of cells
responsible for humoral (antibody)
responses.
These are recognized as a unique and
important part of the immune system with
roles in infectious disease and tumor
surveillance.
NK cells, derived from CD34+
hematopoietic progenitor cells, belong to
13
Hematology PPT Flashcards Unit 3
What are functions of monoclonal antibodies?
What is identified with a monoclonal antibody?
the innate immune system. Unlike T or B
lymphocytes of the adaptive or antigenspecific immune system, NK cells do not
rearrange T-cell receptor or
immunoglobulin genes from their germline
configuration
Monoclonal antibodies to cell surface
antigens now provide a method of
classifying and identifying specific cellular
membrane characteristics
The naming of the surface membrane
antigen is identified with a monoclonal
antibody.
What are functions of T cells?
CD4 T cells play a central role in
immunity. The functions of CD4 T cells
include the following:
Helping B lymphocytes make antibodies
Inducing macrophages to develop enhanced
microbicidal activity
Recruiting neutrophils, eosinophils, and
basophils to sites of inflammation or
infection
Producing cytokines and chemokines to
integrate immune responses
What's the early pre-B cell?
The early pre-B cell is terminal
deoxynucleotidyl transferase
(TDT)-positive and expresses
HLA-DR, CD19, and usually
common ALL antigen (CALLA
[CD10]) antigen.
• The first unique feature that
identifies pre-B cells is the
appearance of immunoglobulin
chains in the cytoplasm.
• Immunoglobulins consist of
light and heavy molecular
weight chains. The heavy
chain (m) of IgM is
synthesized first and
characterizes the pre-B cell.
• Other markers include TDT,
CD19, CD20, CALLA, and HLADR.
Whats the immunoglobulin unique
characteristic of the pre-B cells?
14
Hematology PPT Flashcards Unit 3
What's the functional testing of
lymphocyte cells?
What are the funtions and membrance
characteristics of lymphocytes?
What are the Plasma cell development
and Maturation morphology?
What are the physical characteristic of
th mature B cell after blast
transformation?
In the next stage of maturation,
the early or immature B cell has
cytoplasmic (cIg) and surface
immunoglobulin (sIg) in the form
of complete heavy and light chain
molecules of IgM.
• Functional testing of
lymphocytes
1. Tests of T lymphocyte function
measure mediator production.
Soluble mediators (cytokines)
are secreted by monocytes,
lymphocytes, or neutrophils,
providing the language for
cell-to-cell communication.
• Important cytokines are as
follows:
• Migration inhibition
factor (MIF): affects
macrophage migration
during delayed
hypersensitivity
reactions
• IL-2 (T cell growth
factor): major factor
stimulating T-cell
proliferation
• Chemotactic factor:
attracts granulocytes to
affected areas
•
IL-1: released by
macrophages and activates
helper T cells
• Maturational morphology
• Mature B Cell (after blast
transformation)
• Plasmacytoid
Lymphocytes
•
Plasma cell
• The overall size is 8 to 20 mm.
• The nucleus may be round or
oval and may be eccentrically
placed (not in the middle of
the cell).
15
Hematology PPT Flashcards Unit 3
•

What are the physical characteristics of
plasmacytoid lymphocytes?
•
•
•
•

Where are the plasma cells found and
their physical characteristics?
•
•
•
•
•
The chromatin may be
arranged in a fine pattern.
The cytoplasm is nongranular,
is moderate in amount, and
has a mottled blue color.
The overall size is 15 to 25
mm.
The round or oval nucleus is
eccentrically placed.
The chromatin is coarse and
irregularly spaced.
Nucleoli may be visible.
Usually, the cytoplasm is
distinctive dark blue with a
lighter-staining area, the hof,
next to the nucleus. The hof
represents the area containing
the Golgi apparatus.
The mature plasma cell is not
normally found in peripheral
blood.
About 1% or 2% of plasma
cell−like lymphocytes may be
encountered under stress
conditions.
The overall cell size is 14 to 20
mm.
The nucleus is small and
eccentrically located. More
than one nucleus may be seen
in a cell. The chromatin is
condensed and has a
cartwheel configuration.
Although the cytoplasm is dark
blue, the hof area is usually
visible. The cell has a welldeveloped, rough endoplasmic
reticulum, which is
characteristic of a cell
producing proteins for export.
The distinctive dark-blue
cytoplasm is indicative of
active synthesis and secretion
of proteins (antibodies).
16
Hematology PPT Flashcards Unit 3
What are the characteristics of the
Flame Cell?
Where are the plasma cells disorder
found?
What are the physical characteristics of
Lymphocytes?
Where are lyphocytosis normally found?
Cytoplasm stains a bright-red
color and contains increased
quantities of glycogen or
intracellular deposits of
amorphous matter.
• Not normally found in the
peripheral blood
• In plasma cell dyscrasias, the
plasma cells may be greatly
increased or may completely
infiltrate the bone marrow, for
example, Waldenström
macroglobulinemia and
multiple myeloma.
• The normal range for
lymphocytes in an adult is
22% to 40%, with absolute
values of 1.1 to 4.4 x
109/L.
• Absolute number = total
leukocyte count × relative
% of lymphocytes
A value less than the normal
reference range is called
lymphocytopenia. When the
blood lymphocyte count increases
above the upper limit of the
reference range, the condition is
referred to as lymphocytosis.
• Lymphocytosis is natural
and normal in infants and
children up to approximately
10 years old, with total
lymphocyte counts as high
as 9 x 109/L. This increase
probably results from the
limited production of adrenal
corticosteroid hormones
during this period of the life
cycle. This limited
production of hormones may
underlie the lymphocytosis
seen in later childhood in
conditions such as
•
17
Hematology PPT Flashcards Unit 3
In adults, how are lymphocytosis
change?
What are the malignant conditions that
produce lymphocytosis?
What the the disorders associated with
lymphocytosis?
malnutrition and scurvy.
2. Lymphocytosis is not a
common nonspecific response
to inflammation as is
neutrophilia.
• In adolescence and
adulthood, nonmalignant
conditions associated with
an absolute lymphocytosis
include the following:
• Acute viral infections (e.g.,
infectious mononucleosis,
infectious hepatitis,
posttransfusion syndrome,
CMV infection, and
infectious lymphocytosis)
• Some bacterial infections
(e.g., Bordetella pertussis
infection [whooping cough]
and brucellosis)
• Parasitic infections (e.g.,
toxoplasmosis)
• Drug reactions (e.g., paminosalicylic acid
hypersensitivity and
phenytoin hypersensitivity)
1. Uncommon causes (e.g.,
tertiary and congenital syphilis
and smallpox)
• Malignant conditions that
produce lymphocytosis:
• Lymphocytic leukemia (acute
and chronic forms)
• The leukemic phase of
lymphomas
• Waldenström
macroglobulinemia
•
Cancer
• Infectious mononucleosis
• Cytomegalovirus infection
• Toxoplasmosis
• Infectious lymphocytosis
1. Bordetella pertussis
(Haemophilus pertussis)
18
Hematology PPT Flashcards Unit 3
What is the infectious
Mononucleosis?
What is EBV?

What are the laboratory testing
necessary to esablish or confirm a
diagnosis of infectious
mononucleosis?
•
•
1.
What are the laboratory tests for
infectious mononucleous?
•
infection
• Infectious mononucleosis is
usually an acute, benign,
and self-limiting
lymphoproliferative
condition caused by EpsteinBarr virus (EBV).
EBV is also the cause of
Burkitt lymphoma, a malignant
tumor of the lymphoid tissue
occurring mainly in African
children; nasopharyngeal
carcinoma; and neoplasms of
the thymus, parotid gland, and
supraglottic larynx.
Laboratory testing is necessary
to establish or confirm a
diagnosis of infectious
mononucleosis.
Hematological studies reveal
leukocyte counts ranging from
10 to 20 × 109/L in
approximately two thirds of
patients; about 10% of the
patients with this disorder
demonstrate leukopenia.
A differential leukocyte count
may initially disclose
neutrophilia, although
mononuclear cells usually
predominate as the disorder
develops. Typical relative
lymphocyte counts range from
60% to 90%, with 5% to 30%
variant lymphocytes. These
variant lymphocytes exhibit
diverse morphological features
and persist for 1 to 2 months
in some patients and as long
as 4 to 6 months in others.
If the classic signs and
symptoms of infectious
mononucleosis are absent, a
diagnosis of infectious
19
Hematology PPT Flashcards Unit 3
•
What is Cytomegalovirus Infection?
•
mononucleosis is more difficult
to make.
The diagnosis may be
established by antibody
testing. The antibodies present
in patients with infectious
mononucleosis are heterophil
and EBV antibodies. Rapid
slide tests that use the
principle of agglutination of
horse erythrocytes are
available. The use of horse
erythrocytes appears to
increase the sensitivity of the
test.
• Human CMV is classified as
a member of the herpes
family of viruses. There are
currently five recognized
human herpes viruses:
herpes simplex I, herpes
simplex II, varicella-zoster
virus, EBV, and CMV.
• In patients with CMV
infection, hematological
examination of the blood
usually reveals a
characteristic leukocytosis.
A slight lymphocytosis with
more than 20% variant
lymphocytes is common.
Clinical chemistry assays
may demonstrate abnormal
liver function. Another
assessment of the presence
of infection is the
demonstration of inclusion
bodies in leukocytes in
urinary sediment.
A definitive diagnosis can only
be made by isolating the virus
from urine or blood samples or
by demonstrating CMV-specific
IgM or increasing CMV-specific
20
Hematology PPT Flashcards Unit 3
What is the normal range of lymphocytes with
absolute values?
How is the absolute number of leukocyte
calculated?
What are the terms referring to low and high
number of lymphocytes in the blood?
How is the number of lymphocytes change in
children; and to what conditions lymphocytosis
may relate?
Which is a more common non-specific
response to inflammation? Lymphocytosis or
neutrophilia?
What are the nonmalignant conditions
associated with lymphocytosis in both
adolescence and adulthood?
What are the malignant conditions which
produce lymphocytosis?
IgG antibody titers.
The normal range for lymphocytes in an
adult is 22% to 40%, with absolute values
of 1.1 to 4.4 x 109/L.
Absolute number = total leukocyte count ×
relative % of lymphocytes
A value less than the normal reference
range is called lymphocytopenia. When the
blood lymphocyte count increases above
the upper limit of the reference range, the
condition is referred to as lymphocytosis
Lymphocytosis is natural and normal in
infants and children up to approximately 10
years old, with total lymphocyte counts as
high as 9 x 109/L. This increase probably
results from the limited production of
adrenal corticosteroid hormones during this
period of the life cycle. This limited
production of hormones may underlie the
lymphocytosis seen in later childhood in
conditions such as malnutrition and scurvy.
Lymphocytosis is not as common of a
nonspecific response to inflammation as is
neutrophilia.
In adolescence and adulthood,
nonmalignant conditions associated with an
absolute lymphocytosis include the
following:
Acute viral infections (e.g., infectious
mononucleosis, infectious hepatitis,
posttransfusion syndrome, CMV infection,
and infectious lymphocytosis)
Some bacterial infections (e.g., Bordetella
pertussis infection [whooping cough] and
brucellosis)
Parasitic infections (e.g., toxoplasmosis)
Drug reactions (e.g., p-aminosalicylic acid
hypersensitivity and phenytoin
hypersensitivity)
Uncommon causes (e.g., tertiary and
congenital syphilis and smallpox)
Malignant conditions that produce
lymphocytosis:
Lymphocytic leukemia (acute and chronic
forms)
The leukemic phase of lymphomas
21
Hematology PPT Flashcards Unit 3
What disorders are associated with
lymphocytosis?
What is infectious mononucleosis and what
causes it?
What other conditions does EBV cause in
which ethnic group?
Waldenström macroglobulinemia
Cancer
Infectious mononucleosis
Cytomegalovirus infection
Toxoplasmosis
Infectious lymphocytosis
Bordetella pertussis (Haemophilus
pertussis) infection
Infectious mononucleosis is usually an
acute, benign, and self-limiting
lymphoproliferative condition caused by
Epstein-Barr virus (EBV).
EBV is also the cause of Burkitt
lymphoma, a malignant tumor of the
lymphoid tissue occurring mainly in
African children; nasopharyngeal
carcinoma; and neoplasms of the thymus,
parotid gland, and supraglottic larynx.
Which age group is infectious mononucleosis
the most frequent suggested by three studies?
What diagnostic method is necessary to
establish infectious mononucleosis?
What are the leukocyte counts in what percent
of patients with infectious mononucleosis?
How are the leukocyte counts change with
morphological diversity during the
development of infectious mononucleosis?
Laboratory testing is necessary to establish
or confirm a diagnosis of infectious
mononucleosis.
Hematological studies reveal leukocyte
counts ranging from 10 to 20 × 109/L in
approximately two thirds of patients; about
10% of the patients with this disorder
demonstrate leukopenia.
A differential leukocyte count may initially
disclose neutrophilia, although
mononuclear cells usually predominate as
the disorder develops. Typical relative
lymphocyte counts range from 60% to
90%, with 5% to 30% variant lymphocytes.
These variant lymphocytes exhibit diverse
morphological features and persist for 1 to
2 months in some patients and as long as 4
to 6 months in others.
22
Hematology PPT Flashcards Unit 3
What is a characteristic of infectious
mononucleosis under the microscope?
What happens if the classic signs and
symptoms are absent in infectious
mononucleosis?
What other laboratory methods can be used to
establish the diagnosis?
If the classic signs and symptoms of
infectious mononucleosis are absent, a
diagnosis of infectious mononucleosis is
more difficult to make.
The diagnosis may be established by
antibody testing. The antibodies present in
patients with infectious mononucleosis are
heterophil and EBV antibodies. Rapid slide
tests that use the principle of agglutination
of horse erythrocytes are available. The use
of horse erythrocytes appears to increase
the sensitivity of the test.
What is the order of antibody response to
infectious mononucleosis?
How is the human cytomegalovirus is
classified?
What are the laboratory results which indicate
a CMV infection?
How a definitive diagnosis can be made?
What is the organism which causes
Human CMV is classified as a member of
the herpes family of viruses. There are
currently five recognized human herpes
viruses: herpes simplex I, herpes simplex
II, varicella-zoster virus, EBV, and CMV.
In patients with CMV infection,
hematological examination of the blood
usually reveals a characteristic
leukocytosis. A slight lymphocytosis with
more than 20% variant lymphocytes is
common. Clinical chemistry assays may
demonstrate abnormal liver function.
Another assessment of the presence of
infection is the demonstration of inclusion
bodies in leukocytes in urinary sediment.
A definitive diagnosis can only be made by
isolating the virus from urine or blood
samples or by demonstrating CMV-specific
IgM or increasing CMV-specific IgG
antibody titers.
The microorganism Toxoplasma gondii
23
Hematology PPT Flashcards Unit 3
toxoplasmosis?
How does toxoplasmosis resemble infectious
mononucleosis?
What is a typical sign of toxoplasmosis which
can be seen on a blood smear?
How is the definite diagnosis established?
What is the leukocyte count in infectious
lymphocytosis?
What do the differential peripheral blood
counts show in infectious lymphocytosis?
Which tests are negative in infectious
lymphocytosis?
What are the leukocyte counts of children with
chronic infectious lymphocytosis?
What is the organism which causes whooping
cough?
What are total leukocyte and lymphocyte
counts in whooping cough?
What does the peripheral blood smear show in
whooping cough?
causes toxoplasmosis. Toxoplasma gondii
was recently recognized as a tissue
Coccidia.
Both clinical and laboratory findings in this
disease resemble infectious mononucleosis.
An increased number of variant
lymphocytes can be seen on a peripheral
blood smear.
The diagnosis is established by
serologically demonstrating significant
elevations of Toxoplasma antibodies.
Leukocytosis with lymphocytosis
characterizes this disease. It may precede
clinical manifestations of the disease with
leukocyte counts of 20 to 50 × 109/L.
Differential peripheral blood counts reveal
up to 95% small, mature, normal-appearing
lymphocytes. These lymphocytes are
probably of T-cell origin. No lymphoblasts
are present. An increase in eosinophils may
be noted.
Results of heterophil and EBV antibody
tests are negative.
In children with the chronic form of
infectious lymphocytosis, the leukocyte
count ranges from 10 to 25 × 109/L, with a
predominance of normal-appearing
lymphocytes. Other leukocytic alterations
are minimal.
Whooping cough is caused by B. pertussis,
a bacterial organism that produces
inflammation of the entire respiratory tract.
The total leukocyte count can be increased
to as high as 100 × 109/L, with an absolute
lymphocyte value of as high as 50 × 109/L.
The absolute lymphocyte value is usually
15 to 40 × 109/L. These leukocyte and
lymphocyte values are major laboratory
findings and may be present if the
characteristic cough has not yet developed
or is mild enough to be missed during
physical examination.
On a peripheral blood smear, the
lymphocytes are small and mature, with
only a rare occurrence of lymphoblasts. A
definitive diagnosis can be made on
24
Hematology PPT Flashcards Unit 3
How is lymphocytopenia defined?
How are the immune disorders associated with
lymphocytopenia classified?
What is DiGeorge syndrome and what do
patients with this disorder exhibit?
What is observed regarding the CD4-CD8 ratio
on AIDS?
What are the signs of systemic lupus
erythematosus?
isolation of the bacteria.
Lymphocytopenia is generally defined as
less than 3.0 × 109/L lymphocytes in adults
or less than 1.5 × 109/L lymphocytes in
children.
Immune disorders may be caused by
defects in the numbers or functional
properties of lymphocytes and may be
congenital or acquired. These conditions
are usually classified as either T-cell or Bcell disorders. Some of the less common
disorders involve both T and B cells.
A number of T-cell and B-cell defects
involve the alteration of some lymphocyte
subpopulations. Patients with DiGeorge
syndrome exhibit a decrease in total T
lymphocytes coupled with an increased
ratio of helper to suppressor cells.
In AIDS, a reversed phenotypic CD4-toCD8 ratio due to a decrease in helper cells
is observed.
A decrease in total T cells and a lack of, or
reduced, suppressor cell population are
among the immunological changes
observed in active systemic lupus
erythematosus.
Virchow
Who was the first to recognize leukemia as a
distinct clinical disorder between 1839-1845?
Why did Virchow name the disorder leukemia? because of the white appearance of the
blood from patients with fever, weakness,
and lymphadenopathy
What category are leukemias, lymphomas,
proliferative diseases (neoplasms)
myelomas?
What and where is leukemia?
it is a disease of leukocytes in the blood
and bone marrow
What is lymphoma?
a general term for malignancy that starts in
the lymph system, mainly the lymph nodes
What are the two main types of lymphoma?
Hodgkin’s and non-Hodgkin’s
What is myeloma?
a form of cancer in the plasma cells where
the cells overgrow forming a tumor
What does total leukocyte count determine?
whether a leukemia is acute or chronic
What characteristics do acute leukemias have? symptoms of short duration, many
immature cells forms in the bone marrow
and/or peripheral blood, elevated total
leukocyte count
What characteristics do chronic leukemias
symptoms of long duration, mostly mature
25
Hematology PPT Flashcards Unit 3
have?
What are the differences in the prognoses of
survival in untreated acute forms and chronic
forms?
What system has been enhanced with
molecular information?
What is another form of leukemia
classification?
What are the three types of broad leukemias
using the FAB system?
What are the three lineages for neoplasms
according to the WHO system?
What are classifications based on?
What is the significance of modern drugs on
leukemias and the patients?
How does leukemia develop?
What are some factors that cause leukemias
and lymphomas?
What are the most common types of DNA
changes that can lead to leukemia?
What occurs when part of a chromosome is
lost?
When do inversions occur?
When do additions occur?
When and how is a single oncogene produced?
What are some examples of how cancerpredisposing genes may act?
cell forms in the bone marrow and/or
peripheral blood, and total leukocyte
counts that range from extremely elevated
to lower than normal
several weeks to several months in acute
forms and months to many years in chronic
forms
World Health Organization system
French-American-British (FAB)
classification
myelogenous, monocytic, lymphocytic
myeloid, lymphoid, histiocytic/dendritic
cell
morphology combined with
immunophenotyping and genetic studies of
peripheral blood, bone marrow, and lymph
node samples
They are more effective against malignant
cells and are less toxic to the patient, have a
significant impact on the longevity of
patients with many forms of leukemia and
lymphoma
Subsequent to the malignant transformation
of one or more normal hematopoietic
progenitor cells
Genetic/immunologic factors,
occupational/environmental exposure,
chemical exposure, drug exposure, viral
agents, etc.
translocation
deletions
When part of a chromosome gets turned
around/reversed
When an extra chromosome or part of one
is gained.;
Through mutation in a target cell that is not
sufficient to convert these cells into fullblown cancer cells
they may alter the immune system’s ability
to recognize and wipe out incipient tumors,
they may affect a host’s ability to repair
resulting damage to DNA, etc
26
Hematology PPT Flashcards Unit 3
What are proto-oncogenes?
What are tumor suppressing genes?
What are some examples of diffusible factors?
What is an occupational factor associated with
an increased incidence of leukemia?
Chemical exposure is more strongly linked to
an increased risk of which leukemia?
What is the most common translocation in
ALL adults?
What virus has been linked to ALL?
When does secondary AML develop?
Where are leukemias highest and lowest
incidences?
At what ages are leukemias highest incidences,
and death rates?
Which leukemia is slightly more common in
boys than girls?
What is the male to female ratio in adults for
CLL?
What is the WHO synonym for FAB M6A and
M6B?
What is the median age seen suffering from
Erythroleukemia?
Is Erythroleukemia more prone in male or
females?
What is the average length of survival of
someone having Erythroleukemia?
What is the most common cancer encountered
in children younger than 15?
Does acute lymphoblastic leukemia only affect
children?
central regulators of growth in normal cells
and are antecedents of oncogenes
Also known as antioncogenes; regulators of
the proliferation of cell growth in normal
cells
beta-interferon, tumor growth factor, tumor
necrosis factor
ionizing radiation
Acute myelogenous leukemia
The Philadelphia chromosome, a swapping
of DNA between chromosomes 4 and 11
aka., t(4;11) or 8 and 14 aka., t(8;14)
The Epstein-Barr virus (EBV)?
with a hematologic disorder, with an
inherited disease, with myelodysplastic
syndrome for at least three months, in those
who have been treated with leukemogenic
agents
highest in Scandinavian countries and
Israel, lowest in Japan and Chile
highest incidence among children aged 1-4,
highest death rate among children aged 1519
ALL
2:1
The WHO synonym is acute erythroid
leukemia.
The median age of occurrence is 54 years.
It is more prone for males, having a 1.4:1
male:female ratio.
The average length of survival is 11
months.
Acute lymphoblastic leukemia (ALL) is the
most common cancer in children,
representing 23% of cancer diagnoses
among children younger than 15 years of
age.
No, ALL has a bimodal age distribution,
peaking in children between 3 and 5 years
of age and again in persons older than 65
27
Hematology PPT Flashcards Unit 3
Does ALL affect males more than females? Is
it more prominent in white or black children?
What are the statistics for children to live with
ALL for 5 years? 10 years?
Do adults have the same capability as children
when being diagnosed for ALL?
What are the different classifications for ALL?
What biomarkers can be used to help in
differentiating for ALL?
Proteins expressed on the cell membrane help
aid in the differentiation of what?
What common antigen is found of the surface
of lymphoblasts? What does CD20 indicate?
What is mixed lineage leukemia (MLL) and is
it the same as ALL?
What DNA-based evidence do they have in
order to differentiate MLL from ALL?
Why are cytogenetic studies crucial for the
correct diagnosis of AML or ALL?
years.
Pediatric ALL occurs slightly more often in
boys than in girls and in white children
more often than in black children.
About 85% of children with ALL live for 5
years or more, and 78.1% for 10 years.
Treatment of adults with ALL has lagged
behind the results of treatment achieved
with children.
Acute lymphoblastic leukemia (ALL) is
divided into the following:
-FAB L1 (children)
-FAB L2 (older children and adults)
-FAB L3 (patients with leukemia
secondary to Burkitt lymphoma)
Surface markers, proteins on the cell
membrane that can be detected with
immunologic reagents, are extremely
helpful in differentiating ALL.
Different proteins are expressed at different
stages of maturation, which allows them to
be used as markers of both cell lineage and
maturation.
The common ALL antigen (cALLA) is
found on the surface of lymphoblasts in
70% of patients with ALL. CD20
expression is associated with inferior
survival in adults with ALL.
Mixed lineage leukemia (MLL) has been
established to be a distinct disease and not
a subtype of the prevalent acute
lymphoblastic leukemias (ALL).
Using DNA microarray technology, gene
profiles of more than 12,000 genes
established that about 1,000 genes were
underexpressed and about 200 were
expressed at higher levels in MLL when
compared to ALL. This gene expression
signature distinguishes MLL from classic
ALL.
Cytogenetic studies are important because
two thirds of patients diagnosed with AML
or ALL and 90% of patients with
secondary leukemia will have leukemic
blasts showing clonal chromosomal
abnormalities. Chromosomal abnormalities
28
Hematology PPT Flashcards Unit 3
What gene should be studied in order to
diagnose ALL or CML?
What is a common characteristic within half of
all patients with ALL?
What chromosomal changes are seen within
patients with ALL?
What are some cytochemical stains?
How do the Sudan stains affect the cell?
Why are Sudan stains useful in diagnosing
leukemias?
Where is peroxidase found in the human body?
Is myeloperoxidase only located in primary,
azurophilic granules?
What does the Periodic acid-Schiff measure?
Should neurophils have a large amount of the
measured substance?
Which cells of immunity does PAS not target?
differ between AML and ALL and among
the various subtypes.
The BCR/abl, t(9;22) translocation
qualitative assay by RT-PCR should be
ordered to screen patients suspected of
ALL or CML for the presence of the
bcr/abl transcript.
About half of patients with lymphoblastic
leukemia have abnormal karyotypes.
Gains in chromosome 21 and losses in
chromosome 7, 9, or 20 have all been cited.
Sudan black B, Myeloperoxidase, Periodic
acid–Schiff (PAS), Naphthol AS-D
chloroacetate (NASDCA) esterase, Alphanaphthyl acetate-butyrate esterase with
fluoride inhibition, Leukocyte alkaline
phosphatase (LAP), and Acid phosphatase
with or without tartaric acid inhibition
The Sudan stains, such as Sudan black B,
are substances belonging to a series of
lipid-soluble pigments that detect cellular
lipids.
This procedure is helpful in differentiating
acute myeloid leukemia from ALL.
In humans, peroxidases are found in the
microbodies of liver and kidney cells and
in the granules of myeloid and monocytoid
cells.
No, primitive blasts that are committed to
the myeloid cell line demonstrate
myeloperoxidase activity in areas such as
the endoplasmic reticulum and the Golgi
region.
The periodic acid–Schiff (PAS) reaction is
important in carbohydrate histochemistry.
Positive staining reactions indicate the
presence of glycogen, a polymer of
glucose, and other 1,2-glycol–containing
carbohydrates. Mature neutrophils contain
high levels of cytoplasmic glycogen, which
is physiologically related to the high
energy needs of neutrophils in
phagocytosis.
The PAS reaction is strongly positive in
neutrophilic granulocytes except blast
forms, immature and mature platelets, and
29
Hematology PPT Flashcards Unit 3
Why is the PAS test clinically helpful?
Which non specific esterase enzymes are used
to recognize monocytic cells?
What do alkaline phosphatases do?
How do acid phosphatases affect monocytes
and lymphocytes?
What diagnosis can immunophenotyping by
flow cytometry confirm or establish?
Monoclonal antibodies play an important role
in supplementary differential testing of what
various ailments?
TdT, CD9, and CD79a positive in early B-cell
precursors, hematogones are expressed by?
What is more frequently present in precursor B
cell ALL, CD79 or CD 20?
Which CD marker is positive in the majority of
cases of precursor B-cell ALL and is rare in Tcell ALL?
What two things are usually negative in mature
B-cell ALL
What CD markers are unique to granulocytes
and monocytes.
What are some of the most common lifethreatening emergencies confronting patients
with acute leukemia
In what phase of leukemia is chemotherapy
done?
Is stem cell transplant a viable treatment option
for leukemia patients?
What is produced in large amounts by cells of
erythrocytes in erythroleukemia (FAB M6).
The usefulness of this procedure is in
establishing the negative characteristics of
myeloblastic and monoblastic leukemias
from lymphoblastic leukemias.
The nonspecific esterase enzymes alphanaphthyl acetate and butyrate esterase are
used clinically to recognize cells of
monocytic origin. If the enzyme is of
monocytic origin, it is inhibited by sodium
fluoride.
Alkaline phospha
a discussion of this cytochemical staining
procedure and its clinical applications in
distinguishing between leukemia and a
leukemoid reaction.
Acid phosphatase monocytes demonstrate a
more intense positive reaction than do
neutrophils. Although lymphocytes display
little activity, T cells do exhibit intense
positivity in the Golgi region, whereas B
cells may be positive or negative.
Leukemia
Leukemias and lymphomas
Precursor B cells
CD79
CD10
TdT and CD99
CD11b, CD11c, CD13, and CD14
Infection, bleeding, leukemic infiltration of
organs, metabolic abnormalities,
hyperleukocytosis
Introduction phase
Yes
Proteins
30
Hematology PPT Flashcards Unit 3
MDS, AML, and CML patients?
What are the peptides used in cancer vaccines
combined with to make the vaccine?
What are the cancer vaccines given with?
What is the purpose of giving Montanide and
sargramostim?
How do the cancer vaccines work?
What is the epidemiology of acute leukemias?
What is the relationship between anemia and
acute leukemia?
What is the prognosis of acute leukemia?
What is the French-American-British (FAB)
Categories of acute leukemia?
Montanide
GM-CSF (sargramostim)
They help the immune system respond to
the vaccines
They activate the immune system to make
specialized cells that search out and kill the
MDS, AML, and CML cells containing the
two proteins.
- There were an estimated 44,790 new
cases of leukemia and an estimated 21,870
deaths from leukemia in the United States
in 2009.
- As a group, the acute leukemias are
characterized by the presence of blasts and
immature leukocytes in the peripheral
blood and bone marrow.
- Anemia is usually present. Anemia can be
caused by bleeding and the replacement of
normal marrow elements by leukemic
blasts.
- Although the total leukocyte count is
usually elevated, some patients may
demonstrate normal or decreased leukocyte
counts.
- Thrombocytopenia is also usually present
in patients with acute leukemia.
- Modern treatment methods have produced
a high rate of survival in children.
Significant progress has been made in the
treatment of childhood acute leukemia.
- Treatment for chronic myelogenous
leukemia and chronic lymphocytic
leukemia has achieved impressive results in
adults.
- The best time to achieve the longest
remission and possible cure of acute
leukemia via maximum cell kill is when the
disease is first diagnosed.
• FAB classifications divide acute
leukemias into two major divisions:
– Acute myeloid leukemias
(AMLs)
– Acute lymphoblastic
leukemias (ALLs)
31
Hematology PPT Flashcards Unit 3
•
How does the World Health Organization
(WHO) Categorize acute leukemia?
What are the general characteristics of Acute
Myeloid Leukemias?
What is the genetic difference of Acute
Myeloid Leukemia (AML)?
The system groups
– Acute myeloid leukemias
into nine subtypes (M0
through M7)
ALL into three categories (L1 through L3)
- The underlying rationale behind the WHO
classification is based on defining disease
entities according to the biology of the
disease, increasing the emphasis on
underlying common genetic characteristics
as well as clinical signs and symptoms.
- WHO classifications require the
additional evaluation of the leukemic blasts
by molecular analysis and flow cytometry.
3. - WHO classification of AML
incorporates and interrelates
cellular morphology, cytogenetics,
molecular genetics, and
immunological markers to
structure a classification system
that is universally applicable and
prognostically relevant.
- AML is the most common leukemia
subtype.
- AML is a genetically heterogeneous
clonal disorder characterized by a
maturation block and the accumulation of
acquired somatic genetic alterations in
hematopoietic progenitor cells that alter
normal mechanisms of self-renewal,
proliferation, and differentiation.
- Classification of AML subtypes is
clinically relevant because particular
abnormalities are associated with distinct
clinical behaviorprognosis is favorable
or unfavorable response to treatment.
There are two different subgroup for AML
with genetic differences with disruption
with:
- FLT 3 gene that encodes a type III
receptor tyrosine kinase. FLT3 is known to
be mutated in up to 30% of patients with
AML.
- Core binding factor (CBF) complex, a
transcription factor complex critical for
regulation of hematopoiesis and normal
32
Hematology PPT Flashcards Unit 3
What is the role of micro-RNA with AML?
What is AML?
What is Acute Myeloid Leukemia (FAB M0)?
What is Acute Myeloid Leukemia (FAB M1)?
What is Acute Myeloid Leukemia (FAB M2)?
myeloid development.
These two major subgroups of genetic
disruptions in AML can demonstrate
interaction in initiating and maintaining the
leukemic clone.
- Micro-RNA expression is associated with
cytogenetics, molecular and morphological
alterations, and clinical outcomes in AML.
- Micro-RNAs are naturally occurring 19to 25-nucleotide RNAs cleaved from 70 to
100 nucleotide precursors that hybridize to
complementary mRNA targets and either
lead to their degradation or inhibit their
translation of the corresponding proteins.
Acute Myeloid Leukemia (AML) is
characterized by an increase in the number
of immature cells in the bone and arrest in
their maturation
The subtype M0 consists of
undifferentiated myeloid blasts.
- The WHO synonym for this condition is
acute myeloblastic leukemia without
maturation.
- This form of leukemia is the most
common type of leukemia in children
younger than 18 months of age, but it
typically occurs in middle-aged adults with
a median age of 46 years.
- The typical male:female ratio of FAB M1
is 1:1.
- The median survival time is 3.5 months
after diagnosis.
- The WHO synonym for this disease is
acute myeloblastic leukemia with
maturation.
- Myeloblasts predominate on peripheral
blood smears. The FAB M2 form of
leukemia typically occurs in middle-aged
persons.
- The median age of occurrence is 48 years;
however, approximately 40% of cases
occur in individuals of age 60 years or
older.
- The approximate male:female ratio is
1.6:1.
The median survival time is 8.5 months.
33
Hematology PPT Flashcards Unit 3
What is Acute Promyelocytic Leukemia (FAB
M3)?
- Laboratory findings may be similar to
those of the FAB M2 type.
- In acute promyelocytic leukemia, the
median age of occurrence is 38 years, with
a median survival of approximately 16
months.
- The approximate male:female ratio is 2:1.
- Anemia and thrombocytopenia are
present in most cases. Total leukocyte
counts range from conditions of leukopenia
to leukocytosis. Leukopenia is seen
frequently. Promyelocytes are the
predominating cell type.
Acute Myelomonocytic Leukemia
- Occurrence of this form of leukemia is
(FAB M4)
uncommon in children and young adults.
- The highest frequency of occurrence is in
adults older than 50 years of age.
- The average male:female ratio is 1.4:1.
Most forms of myelomonocytic leukemia
are of the acute form, with the average
length of survival being approximately 8
months.
- In FAB M4, proliferation of granulocytes
and monocytes is characteristic.
Anemia and thrombocytopenia are present.
Acute Monocytic Leukemia (FAB M5)
- Pure monocytic leukemia is uncommon
and constitutes less than 15% of all
leukemias. Two forms exist: FAB M5A
and FAB M5B.
- FAB M5A form is most common in
young adults (median age, 16 years); the
FAB M5B form has a peak occurrence
characteristically during middle age
(median age, 49 years).
- Male:female ratio is about 0.7:1 in the
M5A form; the male:female ratio is
approximately 1.8:1 in the M5B form.
- This form of acute leukemia is very
resistant to therapy; the life expectancy is
short, ranging from 5 to 8 months
depending on the type.
What is the WHO Classification of Tumours of fourth edition, has enhanced the
the Haematopoietic and Lymphoid Tissues?
classification of lymphoid neoplasms by
including immunophenotypic features and
genetic abnormalities to define different
disorders.
34
Hematology PPT Flashcards Unit 3
How are Chronic leukemias generally
characterized
by the presence of leukocytosis with an
increased number of mature lymphocytes,
lymphocytosis, on a peripheral blood film.
How are Malignant lymphoproliferative
disorders are characterized?
What are Both CLL and SLL are neoplasms
composed of?
by an accumulation of lymphocytes.
How is SLL diff from CLL?
SLL is used for nonleukemic patients with
the tissue morphology and
immunophenotype of CLL.
Who does CLL effect?
adults in Western countries, but it is very
rare in far Eastern countries.
almost 7%
How much percent does CLL/SLL accounts
for of non-Hodgkin lymphomas (NHLs) in
biopsies?
What is the median age onset of leukemia?
small B lymphocytes in the peripheral
blood, bone marrow, spleen, and lymph
nodes, mixed with prolymphocytes and
paraimmunoblasts forming proliferation
centers in tissue infiltrates.
is 65 years. This form of leukemia is rare
before age 20 and uncommon before age
50.
Who does leukemia effect most and by how much? More males than females (1.5 to 2.1:1) are
afflicted by the disorder.
Of all hematologic neoplasm, which BLANK has
the hight genetic predisposition and by how much?
CLL has the highest genetic predisposition
of all hematologic neoplasms. A family
predisposition can be documented in 5% to
10% of patients with CLL. The overall risk
is two to seven times greater in first-degree
relatives of CLL patients.
What type of disorder is CLL?
What percent of lymphoid neoplasms worldwide
do mature B-cell neoplasms comprise?
What is B-CLL?
B-cell disorder
90%
How are B-CLL cells characterized?
A biologically and clinically heterogeneous
hematologic malignancy characterized by a
gradually progressive accumulation of
morphologically mature B lymphocytes in
the blood, bone marrow, and lymphatic
tissues.
As CD5+, CD19+, and CD23+ monoclonal
B cells.
35
Hematology PPT Flashcards Unit 3
What is an excess of B cells likely to be a result
of?
The anti-apoptotic BCL2 gene is reported to be
overexpressed in what percent of B cells?
CLL is heterogeneous on what levels?
Chromosomal alterations occur in what percent of
CLL cases?
What do those alterations include?
decreased apoptosis and deregulation of
cell cycle control
65%-70%
Clinical, cellular, and molecular
80%
The 13q deletion, the 11q deletion, trisomy
of chromosome 12, and the 17p deletion.
What does The high rate of recurrence of the same That these abnormalities may affect a
chromosomal abnormalities suggest?
common pathway.
What are the two major applications in the analysis Demonstration of the clonal nature of a
of chronic lymphoid malignancies?
population of lymphoid cells and Detection
of pathogenetically important
rearrangements, for example, clonal IG or
TCR gene rearrangements, that are useful
in diagnosis of CLL
Why is the IgVH mutational status important?
Important in determining the prognosis of
patients with CLL
What is ZAP-70?
Zeta-chain, associated protein 70
What was recently discovered about ZAP-70?
Recently discovered to be differentially
expressed in the CLL subgroup without
IgVH mutation that had poor outcomes.
How is thymidine kinase significant?
A new finding has shown a correlation of
the serum value of thymidine kinase with
IgVH gene mutational status and also with
disease progression
What is CD38?
Expression of CD38, a membrane protein
that marks cellular activation and
maturation and that has signaling activity
What does the expression of CD38 correlate with
the presence of IgVH mutations
How are microRNA expression profiles used?
To distinguish normal B cells from
malignant B cells in CLL patients
What do microRNAs regulate?
The expression of protein-coding genes and
can act as oncogenes, tumor suppressors, or
both
What do alterations in CLL affect?
Evasion of apoptosis, Self-sufficiency in
growth, and Stimulation of angiogenesis
and dissemination.
What is evasion of apoptosis associated with?
overexpression of the antiapoptotic protein
BCL2.
What is BCL2 responsible for?
maintaining the delicate homeostasis
between proliferation and apoptosis and
promotes cell survival by inhibiting cell
death.
What does self-sufficiency in growth demonstrate? that normal cells require growth stimuli
36
Hematology PPT Flashcards Unit 3
What are the staging classifications?
What do Parameters with demonstrated
independent prognostic values include?
How is CLL usually discovered and why?
Findings on what test typically suggest that the
disease is present?
Excess lymphoid production crowds out what
elements?
How?
compared to cancer cells that are capable of
generating their own growth signals
without having to rely on mitogens in the
surrounding environment in order to
actively proliferate.
− 0—Bone marrow and blood
lymphocytosis
− I—Lymphocytosis with
enlarged nodes
− II—Lymphocytosis with
enlarged spleen or liver or
both
− III—Lymphocytosis with
anemia
IV—Lymphocytosis with
thrombocytopenia
– Number of lymphocytes in
the peripheral blood
– Degree of bone marrow
infiltration
– Proportion of abnormal
lymphoid cells in the
peripheral blood
– Lymphocyte doubling time
– Immunoglobulin heavychain variable-region gene
mutation status
– Cytogenetic abnormalities
assessed by fluorescent in
situ hybridization
• Z-chain–associated protein
kinase-70 protein expression
– At the time of a routine
physical exam because it is
asymptomatic
– On a CBC
–
Normal bone marrow
–
By packing of the bone
marrow space by malignant
lymphocytes.
Anemia, thrombocytopenia,
and neutropenia
Total leukocyte counts can
range from 30 to 200 x
What does this result in?
–
What is the range for total leukocyte counts?
–
37
Hematology PPT Flashcards Unit 3
109/L
What percentage of small lymphocytes are
exhibited in peripheral blood smears with Chronic
Lymphocytic Leukemia (CLL)?
80-90%
Why are many of the cells in peripheral blood
smears look overly mature in Chronic Lymphotic
Leukemia Patients?
What are typically seen in peripheral blood smears
of CLL Patients?
In peripheral blood smears of CLL patients, what
are normal levels?
What is hyper leukocytosis?
Because they have hypercondensed nuclear
chromatin pattern.
What are curative and non-curative treatment
options for CLL patients?
Allogeneic hematopoietic stem cell
transplantation (alloHSCT) is the only
potentially curative treatment available for
patients with B-cell CLL.
How does one asses minimal residual disease in
CLL patients?
How is Hairy Cell Leukemia (HCL) diagnosed?
Which sex is HCL much more common to occur,
and why ?
What age does HCL usually occur?
Smudge Cells.
Granulocytes and Platelets
An elevated leukocyte concentration in a
centrigued peripheral blood specimen from
a patient with T-cell acute lymphoblastic
leukemia
chemoimmunotherapy is an non-curative
treatment that incorporates the use of
monoclonal antibodies to chemotherapy.
Real time PCR and Flow Cytometry based
assays.
Hairy Cell Leukemia is a mature B-cell
malignancy that is diagnosed based on
clinical features, morphology, and
phenotyping.
It is much more common in females due to
a possible involvement with the X
chromosome.
HCL usually occurs after 30 years of age.
How did Hairy Cell Leukemia got its name?
HCL is so named because of the
appearance of fine, hair-like, irregular
cytoplasmic projections that are
characteristic of lymphocytes in this
disease.
Which organs do Prolymphocytic Leukemia
usually affect?
B-cell Prolymphocytic Leukemia
represents a malignancy of B
prolymphocytes affecting blood, bone
38
Hematology PPT Flashcards Unit 3
How is Prolymphocytic Leukemia characterized?
marrow, and spleen.
Prolymphocytic leukemia is characterized
by a large number of small lymphocytes
with scant cytoplasm and the immature
features of prolymphocytes in the
peripheral blood.
In Prolymphocytic Leukemia Leukocytes and
Prolymphocytes can exceed to?
100 × 109/L for Leukocytes and
Prolymphocytes must exceed 55% of
lymphoid cells in the peripheral blood.
What are plasma cell neoplasms?
Multiple Myeloma and Waldenström
primary macroglobulinemia
What is multiple myeloma?
Multiple myeloma is a malignant bone
marrow–based plasma cell neoplasm
associated with abnormal protein
production.
How much does multiple myeloma account for in
all malignancies and all hematological
malignancies?
Multiple myeloma accounts for
approximately 1% of all types of malignant
diseases and about 10% of hematological
malignancies.
What is present in 2/3 of patients with multiple
myeloma?
Anemia is present at the time of diagnosis
in approximately two thirds of patients.
What happens in rare terminal cases of multiple
myeloma?
In rare cases in the terminal stages, plasmablasts
and plasma cells may amount to 50% of the
leukocytes in the peripheral blood. Rouleaux
formation on peripheral blood smears is
common.
What is the leukocyte and lymphocyte count look
like with multiple myeloma?
The leukocyte count can be normal,
although about one third of patients have
leukopenia. Relative lymphocytosis is
usually present. Sometimes, eosinophilia is
noted.
How do the platelets look like for patients with
multiple myeloma?
Platelet abnormalities, impaired
aggregation of platelets, and interference
with platelet function by the abnormal
monoclonal protein contribute to bleeding.
Why is bleeding common in multiple myeloma?
Bleeding is common due to inhibition of
coagulation factors and thrombocytopenia
39
Hematology PPT Flashcards Unit 3
from marrow infiltration of plasma cells or
chemotherapy.
What coagulation factors are increased during
multiple myeloma?
Fibrinogen and Factor VIII
What does electrophoresis of serum from myeloma Increased IgM production, IgG, and less
patients reveal?
frequently IgA. Increased production of
IgD is rarely seen.
What are current treatments for multiple myeloma? Thalidomide, lenalidomide, and
bortezomib are used for newly diagnosed
patents. Chemotherapy cannot cure
multiple myeloma
Waldenström Primary Macroglobulinemia usually
appear in what sex, age-range, and race?
What are the prognostic factors for Waldenström
Primary Macroglobulinemia patients?
Usually found in older men. The median
age of onset varies between 63 and 68
years of age and the incidence of is higher
among whites.
Prognostic factors include the patient’s age,
β2-microglobulin level, monoclonal protein
level, hemoglobin concentration, and
platelet count.
What is the reported median survival for patients
with Waldenström Primary Macroglobulinemia.
The reported median survival of patients
with WM ranges between 5 and 10 years
from the time of diagnosis.
How is Waldenström Primary Macroglobulinemia
characterized?
WM is a B-cell neoplasm characterized by
lymphoplasma proliferative disorder with
infiltration of the bone marrow and a
monoclonal immunoglobulin M (IgM)
protein.
What is the most consistent feature of the bone
marrow and lymph nodes of Waldenström Primary
Macroglobulinemia patients?
It’s the presence of pleomorphic B-lineage
cells at different stages of maturation.
What is the viscosity of the samples of patients
with Waldenström Primary Macroglobulinemia?
Blood samples of patients with
Waldenström Primary Macroglobulinemia
exhibit hyperviscosity.
serum protein electrophoresis (SPEP) and
immunoelectrophoresis (IFE)
How does one detect monoclonal gammopahties in
patients with Waldenström Primary
Macroglobulinemia?
What are the cryoglobulins in Waldenström
Primary Macroglobulinemia samples ?
IgM and IgG
40
Hematology PPT Flashcards Unit 3
What is the solid tumor counterpart of stem cell
leukemia?
Undifferentiated Lymphoma.
What is the solid tumor counterpart of monocytic
leukemia?
What is the relationship between Lymphomas and
Leukemias?
What are some characteristics of Lymphomas?
Reticulum cell sarcoma.
What is Malignant Lymphoma?
What is Myeloid System?
What is the Lymphoid
What are two major forms of Malignant
Lymphomas?
What is NHL?
What is a rare forms of Lymphoma?
What is Pathophysiology?
he neoplastic cells of these two disorders
are identical.
Are a group of closely related disorders
that characterized by the overproliferation
of one or more type of cells of the
lymphoid system such as lymphoreticular
stem cells, lymphocytes, reticulum cells,
and histiocytes.
Malignant Lymphoma expresses itself as a
disorder of the lymph nodes.
Immature white blood cells for example,
blast, pro, myelo, meta, reticular, band, and
mature white blood cells.
Are B-cells and T-cells
Hodgkin and Non-Hodgkin (NHL)
Non-Hodgkin Lymphoma (NHL) account
for more than two thirds of lymphomas and
more than 75% of fatalities due to
lymphoma.
A rare forms of lymphoma include Burkitt
lymphoma
And mycosis fungoides, a variant of Sezary
syndrome, which
Demonstrates skin involvement.
• Although the etiology of most
lymphomas is unknown, the
potential role of a virus in the
pathogenesis of lymphomas is
strongly suspected.
• In humans, the development of B
cells in the bone marrow is initiated
by the assembly of genes for the
variable regions of the heavy and
light chains of antibodies in B-cell
progenitors, mediated by a process
called V(D)J recombination.
In this process, the DNA located between the
rearranging gene elements is deleted from the
chromosome (or sometimes inverted).
41
Hematology PPT Flashcards Unit 3
What is Etiology?
What is Pathogenesis?
What is Hodgkin Disease?
What are Reed-Sternberg Cells?
What is Non-Hodgkin Lymphoma (NHL)?
What are the characteristics of NHL?
What is cytogenetic analysis?
What is Sézary Syndrome?
What was the Ph1 chromosome?
What is the abl gene product ?
What CML is the best characterized leukemia at?
cause of diseases
The origin of disease
Cytogenetic studies now suggest
that Reed-Sternberg cells arise from
a single clone, a common B-cell
precursor located in a germinal
center.
Reed-Sternberg cells are a defining
feature of Hodgkin disease, but less
than 1% of cells in a sample of
Hodgkin disease tissue are ReedSternberg Cells.
• The most frequent type of NHL is
diffuse large B-cell lymphoma,
which accounts for approximately
40% of new cases of lymphoma.
More than half of patients with
diffuse large B-cell lymphoma are
older than 60 years of age.
3) In NHL, Reed-Sternberg cells are
absent. The infiltrating cells may be
of one type or may have a mixed
cell population of lymphocytes,
histiocytes, eosinophils, and some
plasma cells.
4) The chromosomal anomalies that
have been observed in
hematological malignant disease
include structural rearrangement as
translocations and deletions and
numerical abnormalities with
respect to structural rearrangements.
5) The leukemic phase of cutaneous Tcell lymphoma, mycosis fungoides,
is called Sézary syndrome.
It was the first aberrant chromosome
described in a malignant disorder.
The majority of Ph1-positive patients have
the typical t(9;22) translations.
A protein tyrosine kinase, and the fusion
protein bcr-abl has constitutive kinase
activity that deregulates signal transduction
pathways, causing abnormal cell cycling,
inhibition of apoptosis, and increased
proliferation of cells.
A molecular level.
42
Hematology PPT Flashcards Unit 3
What express patients with CML and acute
lymphoblastic leukemia?
What oncogene is activation by?
Chronic myelogenous leukemia.
What reason is detecting gene rearrangements
involving the BCR and C-ABL genes?
Which the clinical course of CML can be
characterized by three separate progressive
phases?
What is Initial phase?
What is Accelerated phase?
What is blast crisis (acute)
The BCR gene rearrangementthe
molecular counterpart of the Ph1
chromosome.
Chromosomal translocation.
Breaks at the ends of the long arms of
chromosomes 9 and 22 allow reciprocal
translocations to occur. The c-abl
protooncogene on chromosome 9 is
translocated to the breakpoint region (bcr)
of chromosome 22. The result is the
Philadelphia chromosome, which contains
a new fusion gene coding for a hybrid
oncogenic protein (bcr-abl), presumably
involved in the pathogenesis of chronic
myelogenous leukemia
– Confirmation
of
Ph1positive cases of CML
– Diagnosis of Ph1-negative
cases of CML
– Diagnosis
of
CML
presenting in blast crisis
– Monitoring of patients with
CML during and after
therapy for the detection of
minimal residual disease
– Confirmation of remission
– Early detection of relapse
-
Initial phase
Accelerated phase
a. Blast crisis (acute)
a) Onset of the early, initial phase
(chronic phase) of CML is insidious
and may last for 3 to 5 years. Most
cases (85%) are diagnosed in this
phase.
b) Transitional, accelerated period
may precede blast transformation.
This transition is heralded by a
rising peripheral blood leukocyte
count, an increased percentage of
basophils, worsening anemia, and
thrombocytopenia.
c) it is characterized by the appearance
of primitive blast cells similar to
those seen in acute leukemia
43
Hematology PPT Flashcards Unit 3
What is Myeloproliferative neoplasms (MPNs)?
They are interrelated clonal hematopoietic
stem cell disorders characterized by
excessive proliferation of one or more
mature myeloid cell lines, for example,
granulocytes,
erythrocytes,
megakaryocytes, or mast cells.
What distinguishes MPNs from other neoplasms?
The discovery of mutations in crucial genes
What is now being incorporated into the diagnostic Molecular analysis
workup of MPNs?
What are one or more shared features of the
multipotent hematopoietic stem cells (CD 34) in
MPNs
Which of the following MPNs characteristics
is also known as agnogenic myeloid metaplasia
or myelofibrosis with myeloid metaplasia ?
1) Cytogenetic abnormalities
2) Overproduction of one or more types of
blood cells with dominance of a
transformed clone
3) Hypercellular marrow or marrow
fibrosis
4) Thrombotic and/or hemorrhagic
bleeding
5) Extramedullary hematopoiesis
6) Transformation to acute leukemia
Primary myelofibrosis
1. Choronic myelogenous leukemia (CML)
2. Polycythemia rubra vera
3. Primary myelofibrosis
4. Essential thrombocythemia
2008 who classification of myeloid Neoplasms
?
What is the primarily neoplasms age of MPNs
in adults ?
What is the spent phase found in
myeloproliferative disorder ?
What condition do myeloproliferative
disorders transform to ?
A mutation in Jak2 is associated with which
types of myeoloproliferative conditions?
Is maturation in –tact in myeloprolife rative
disorder?
Descrive chronic myelogenous leukemia
(CML)
Tyrosine kinase mutation
Janus kinase mutation
50 to 70
It is the halting of all blood cell production
in the marrow and the increase in fibrosis
Acute leukemia
Polycythemia vera, essential
thrombocythemia,
Primary myeolfibrosis
Yes there is effective maturation leading to
increased peripheral blood counts
Is an MPN that originates in an abnormal
pluripotent bone marrow stem cell and is
consistently associated with the BCR –ABL 1
44
Hematology PPT Flashcards Unit 3
What are the other principal types of chronic
leukemia ?
What two genes are commonly mutated in
primary myelofibrosis?
True or false ? CML is a clonal proliferative
disorder of the pluripotent hematopoietic
progenitor cell that resulrs in a disordered
proliferation of cells
What is CML characterized by ?
Excessive increase in mostly mature myeloid
cell in peripheral blood id the ________ of the
intioal (chronic) phase of CML
what is the median age of diagnoses for
chronic Myelogenous Leukemia ?
True or false in CML males a slightly greater
rate of disease occurrence?
What causes unregulated cell overproduction
in chronic Myelogenous leukemia ?
What is the name of the chromosome that
originates in an abnormal pluripotent bone
marrow stem cell and is consistently associated
with the BCR-ABL 1 fusion gene ?
What are the clinical fetures of chronic
myelogenous leukemia ?
Approximately ________of patients whose
illness transforms into acute leukemia develop
myelogenous leukemia
What are some diagnostic coagulation
abnormalities ?
During allogeneic bone marrow
transplantation, what is induced by high-dose
chemoradiotherapy?
Describe alloimmune graft versus leukemia (GvL)
effect?
fusion gene located in the Philadelphia
chromosome
CML and chronic lymphocytic leukemia
Activating JAK2 mutations and MPL
True
Chronic, indolent disease course that
frequently transforms into a terminal, acute
blast crisis phase
Hallmark
50-60
True
Increased tyrosine kinase activity
Philadelphia chromosome
Fatigue
Two thirds
Prolonged activated partial thromboplastin
time (APTT) and significantly decreased level
of factor V
Myeloablation
Mediated by donor T-lymphocytes
What is crucial for identifying disease stage and
progression as well as response to therapy?
Patient monitoring at the cytogenetic and
molecular levels
Patients who achieve complete marrow
cytogenetic remission should still be checked at
__(a)_____ and in the face of ___(b)___.
a) Intervals
Rising blood bcr-abl transcript levels.
45
Hematology PPT Flashcards Unit 3
Polycythemia vera (PV), essential thrombocytosis
(ET), and primary myelofibrosis (PM) are what?
a)
Clonal disorders of multipotent hematopoietic
progenitors.
Polycythemia Rubra Vera is?
A primary disorder characterized by
extremely increased red cell mass.
b)
What is the number of incidences PV effect?
What is the median age at which PV is diagnosis?
What gender does PV primarily effect?
What seems to increase the risk of PV?
PV is a clonal hematopoietic progenitor cell
disorder with?
A very slow evolution of the malignant erythroid
clone leads to what?
What gene has been described in neutrophils of
patients with PV?
True or False: Plethora is the hallmark of PV?
Which disease occurs in more than 75% of
patients?
True or False: Irreversible, moderate hypertension
rarely occurs as the result of the expanded blood
volume.
Which percentage of patients report neurological
symptoms?
What are complications of Polycythemia Rubra
Vera (PV)?
Characteristics of PV are:
What is the treatment for PV?
What is the median survival time for untreated
symptomatic patients after diagnosis?
What is the median survival time with treatment?
Which disorder is characterized by systemic bone
marrow fibrosis and extramedullary
hematopoiesis?
What characterizes secondary myelofibrosis?
2.3 per 100,000 people
60 years old
Male
Exposure to radiation, benzene, and
petroleum refineries
Trilineage hyperplasia; the most constant
and striking feature is erythroid hyperplasia
of the bone marrow.
Overexpansion of the red cell mass,
hypervolemia, and splenomegalic red cell
pooling.
PV-1 gene
TRUE
Splenomegaly
FALSE
50% to 80%
Thrombosis and paradoxical hemorrhage
Increased erythrocyte cell count, packed cell
volume
and hemoglobin with normal erythrocytic
indices
Therapeutic phlebotomy, drug therapy
6 to 18 months
More than 10 years
Primary myelofibrosis
Infiltrative disorders, including malignancies and
infections, or exposure to chemical toxins or
irradiation.
True or False: Primary myelofibrosis is uncommon TRUE
About what percentage of patients with PV
20.00%
46
Hematology PPT Flashcards Unit 3
develop myelofibrosis?
What happens to patients with myelofibrosis?
What is primary myelofibrosis
What is the % of patients acquired recurrent
cytogenetic abnormalities?
What are the clinical signs and symptoms of
myelofibrosis?
Explain the cellular alterations in myelofibrosis
What have been identified as factors with
prognostic significance in patients with primary
myelofibrosis ?
What is the median survival time ranges?
What are some of the treatments of myelofibrosis?
Describe Essential or primary thrombocythemia
and the causes
They may undergo temporary or permanent
transition to PV or may convert to CML.
Primary myelofibrosis is a clonal disorder
of the multipotential progenitor cell
compartment.
Dysmegakaryocytopoiesis leading to an
overproduction of defective platelets is the
most constant feature of myelofibrosis.
Approximately 40% of patients acquire
recurrent cytogenetic abnormalities and
nearly 80% acquire nonspecific
aberrations.
Patients with myelofibrosis usually exhibit
progressive anemia, splenomegaly, and
marrow fibrosis.
The leukoerythroblastic picture of teardropshaped erythrocytes, nucleated
erythrocytes, and immature myeloid cells is
classic for myelofibrosis.
Leukocytosis, mild anemia,
thrombocytosis, and panhyperplasia in the
marrow are characteristic in the early
stages.
Extramedullary hematopoiesis, peripheral
cytopenias, and myelofibrosis reflect the
changes seen in the later stages.
Transitions among the different types of
MPNs and termination in acute leukemia or
marrow failure are common
hemoglobin concentration, platelet count,
and the presence of osteomyelosclerosis
The median survival time ranges from 4.3
to 5.0 years.
Treatment of myelofibrosis can consist of
periodic transfusions of packed red blood
cells, androgens, cytotoxic agents, and
platelet reduction by plateletpheresis.
Essential or primary thrombocythemia is
characterized by a significant increase in
circulating platelets, usually in excess of
1,000 x 109/L.
Elevated platelet counts may be
encountered as a reactive phenomenon,
47
Hematology PPT Flashcards Unit 3
What is a usual lab finding when dealing with
essential thrombocythemia?
How are peripheral blood erythrocytes frequently
described as during essential thrombocythemia?
If splenic atrophy is present, during essential
thrombocythemia, abnormal morphology includes:
In more than half of patients with
thrombocythemia, the platelet-rich plasma does not
respond to epinephrine.
By what characteristic can thrombocythemia and
polycythemia vera be differentiated?
secondary to a variety of systemic
conditions, or they may represent essential
thrombocythemia, a primary disorder of the
bone marrow.
Significantly elevated peripheral blood
platelet count, usually in excess of 1,000 x
109/L, with a minimum of 600 x 109/L
Hypochromic and microcytic
 Target cells
 Howell-Jolly bodies
 Nucleated erythrocytes
Acanthocytes
4) Epinephrine
5) The absence of an expanded red
blood cell mass in
thrombocythemia.
The chronic leukemias are usually characterized by leukocytosis
the presence of what?
The total leukocyte count is usually greater than
50x109/L and may exceed 300 x 109/L.
what amount?
Peripheral blood smears demonstrate increased
segmented neutrophils and band forms, and
numbers of mature granulocytic forms. What type smaller numbers of immature forms.
of granulocytic forms are observed?
Cytochemical studies are used less frequently for
acute leukemias.
chronic leukemias than for what other type of
leukemia?
In special cases, leukocyte alkaline phosphatase
a leukemoid reaction
(LAP) procedure is used to differentiate between
CML and what other type of reaction?
In CML, the LAP score is (decreased or increased decreased
)as compared with a leukemoid reaction, in which
a high score is usual.
Because chronic-phase CML is highly responsive
one
to treatment, many patients experience at least how
many remissions?
Remissions can last from several weeks to months,
with 60% of patients becoming what?
The introduction of imatinib has fundamentally
altered the management of patients with CML in
what phase?
It is recommended as the best single agent for
newly diagnosed patients who are not eligible for
asymptomatic
Chronic phase
Stem cell
48
Hematology PPT Flashcards Unit 3
initial treatment by allogeneic what type of cell
transplantation?
A long-standing and universally accepted therapy
for CML is allogeneic stem cell transplantation
(allo-SCT). Allo-SCT achieves its curative
potential via at least how many mechanisms?
How is Myelodysplastic Syndrome (MDS)
characterized?
What is included in the classification
Myelodysplastic/Myeloproliferative Neoplasm
(MDS/MPN)?
What is usually demonstrated in patients placed in
the MDS/MPN category, as in chronic
myelomonocytic (CMML)?
The MDSs and MDSs/MPNs are a heterogeneous
group of clonal disorders of what?
True or False
The clonal nature of MDS is supported by research
studies, even in the absence of detectable
cytogenetic abnormalities.
True or False
The MDSs are classified into various types of
refractory anemias, one of the included subtypes is
Refractory anemia with excess of sideroblasts
(RAEB-1 and RAEB-2)
What occurs without a known history of
chemotherapy or radiation exposure?
___________MDS can sometimes be directly
related to a known agent.
What are the risk factors may be possible
etiologies for developing MDS?
Two
MDS is characterized by the simultaneous
proliferation and apoptosis of hemopoietic
cells that lead to a normal or hypercellular
bone marrow biopsy and peripheral blood
cytopenia.
Clonal myeloid neoplasms that at initial
presentation have some clinical, laboratory,
or morphologic findings that support a
diagnosis of MDS and other findings that
are more consistent with MPN.
Hypercellular bone marrow because of
proliferation of one or more cell lines
Bone marrow
True
False (Refractory anemia with excess of
blasts (RAEB-1 and RAEB-2)
Primary or de novo MDS
Secondary
Age, Genetic predisposition,
Environmental exposure, prior therapy,
other factors( eg. Abuse of drugs, OTC
drugs)
Myelodysplastic Syndromes
Exposure particularly with benzene and possibly
other industrial solvents may be a possible etiology
for developing what syndrome?
Fanconi anemia, Shwachman-Diamond syndrome, Myelodysplastic Syndromes
and Diamond-Blackfan syndrome are associated
with an increased risk of what syndrome?
True or false
False (rare in childhood)
MDS is rare in adult.
49
Hematology PPT Flashcards Unit 3
MDS is more common in males or females?
True or False
The adult form usually occurs in persons older
than 50 years of age (most patients are 60 to 75
years old).
What chromosomes are mainly involved in
characteristic karyotype anomalies?
Survival of patients with MDS is better for those
with what chromosomal patters?
What are the clinical signs and symptoms that
maybe reported by a patient with MDS?
In MDS, what causes the infections?
Dysfunctional granulocytic neutrophils or absolute
granulocytopenia causes what?
What causes the hemorrhages that occurs in
patients with MDS?
What is the common initial presenting symptom in
MDS?
Laboratory manifestations of MDS
include________,________, and _________.
a. Anemia
b. Low platelet count
c. Low total leukocyte count
d. All of the above
Another MDS laboratory manifestation
includes____________.
a. Poikilocytosis
b. Microcytic anemia
c. Macrocytic anemia
d. Absolute Nuetropenia
Peripheral blood smears _________ exhibit red
blood cell abnormalities and large
dysfunctional platelets in MDS.
a. rarely
b. frequently
c. mostly
d. always
RA is one of the refractory cytopenias
with___________ dysplasia, is the mildest
form of all types of MDS. Fill in the blank.
a. Unilineage
b. Multilineage
c. Omnilineage
Males
True
Chromosomes 5, 7, and 8.
Normal chromosomal patterns
History of infections, bleeding, weight loss,
or cardiovascular symptoms may be
reported by a patient
Infections are caused by dysfunctional
granulocytic neutrophils or absolute
granulocytopenia.
Infections
Decreased or dysfunctional platelets
Anemia
D
D
A
50
Hematology PPT Flashcards Unit 3
d. monolineage
RARS has the presence of sideroblasts. True or
False
RAEB-1 and RAEB-2 have the presence of
type 1 and Type 2 myeloblasts in bone marrow
and in blood. Tue or False
Chronic myelomonocytic leukemia (CMML) is
a ________ hematologic malignancy that is
characterized by features of both an MPN and
an MDS.
a. Polyclonal
b. Monoclonal
c. Clonal
d. Uniclonal
CMML is less frequent than the _______
variety.
a. Chronic
b. Acute
c. Malefic
d. Asymptomatic
In the Diagnosis of CMML, according to the FAB
classification criteria, distinguishes between two
forms, CMML-1 and CMML-2. True or False
The hallmark of CMML are Peripheral blood
smears usually demonstrate a persistent monocyte
count greater than 1 × 109/L. True or False
CMML does not include Nuetrophilia as a
commonly observed hallmark. True or False
One of the most widely used prognostic systems
for MDS patients is the International Prognostic
Scoring System (IPSS). A score of more than or
equal to 2.5 is considered high risk. True or False
False, it has ringed siderblasts
True
C
B
True
True
False
True
51