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The State Education Institution of Higher Professional Training
The First Sechenov Moscow State Medical University
under Ministry of Health of the Russian Federation
Department of Pathophysiology
Malignancies of
hematopoietic cells.
Leukemia
Lecture presentation
Professor Pirozhkov S.V.
2015-2016 education year
Causes of hematopoietic cell malignancies
■ Inherited genetic factors
- Fanconi anemia
- ataxia-telengiectasia
- Down syndrome
■ Chemical agents
-
benzene
components of cigarette smoke
petroleum products
herbicides, pesticides
■ Viruses
- Human T-lymphocyte leukemia virus I (HTLV-1)
- Epstein-Barr virus
- Human herpesvirus 8
■ Physical factors
- ionizing radiation
■ Iatrogenic factors
- radiotherapy
- chemotherapy
Classification of the hematopoietic cell
malignancies
I.
Lymphoid neoplasms
● Lymphoid leukemias
(originate in the bone marrow)
● Lymphomas
(reside predominantly in lymphoid tissue)
II. Myeloid neoplasms
(arise in hematopoietic stem cells that give rise to
cells of the myeloid lineage)
GENERAL CHARACTERISTICS OF LEUKEMIA
● Atypia of neoplastic blood cells
● Coexistence of two lines of hematopoietic cells
of the same type: normal and transformed
● Impairment of differentiation of tumor cell line
leading to the emergence of immature cells in
the peripheral blood
● Crowding out of normal population of cells by
tumor cells
● Leukemic picture of the peripheral blood
LEUKEMIC PERIPHERAL BLOOD PICTURE
● Leukocytosis (typical)
● Increase in young cells count, emergence of
immature forms including blast cells (shift to
the left)
● “Hiatus leukaemicus” (in case of acute
myeloid leukemia)
● Eosinophillic-basophillic association (in case
of chronic myeloid leukemia)
● Anemia
● Thrombocytopenia
TYPES OF LEUKEMIC PERIPHERAL BLOOD PICTURE BASED
ON LEUKOCYTE COUNTS AND THE PRESENCE OF BLAST
CELLS
1. Leukemic leukemia – leukocyte counts exceed
50,000 or 80,000 cells/μl; blast cells are abundant.
2. Subleukemic leukemia – leukocyte counts are
below 50,000 cells/μl; blast cells are abundant.
3. Leukopenic leukemia - leukocyte counts are
below the normal value; blast cells are present.
4. Aleukemic leukemia – normal picture of the
peripheral blood; malignant cells can be found only in
the bone marrow.
MECHANISMS OF ANEMIA IN LEUKEMIA
● Crowding out of normal erythropoietic stem
cells and their progenitors by tumor cells
● Competition between malignant and normal
cells for substrates and vitamins, including B12
and folic acid
● Production of antibodies or sensitized T-killers
against normal erythrocytes (in chronic
lymphocytic leukemia)
● Myelofibrosis with pancytopenia in late stages
of chronic myeloproliferative diseases
GENERAL CHARACTERISTICS OF ACUTE
LYMPHOBLASTIC LEUKEMIA AND LYMPHOMA (ALL)
● Neoplasm is composed of immature precursor
B (pre-B) or T (pre-T) lymphocytes referred to as
lymphoblasts
● The majority of ALL (~85%) are pre-B tumors
that typically manifest as childhood acute
leukemia
● The less common pre-T cell ALLs tend to
present in adolescent males as lymphomas,
often with thymic involvement
● The bone marrow and the peripheral blood
contain > 20% lymphoblasts
PERIPHERAL BLOOD FINDINGS IN ACUTE
LYMPHOBLASTIC LEUKEMIA
● At least 20% lymphoblasts in the peripheral
blood; the phenotype of lymphoblasts in most
common children precursor B-lymphoblastic
leukemia: TdT+ (terminal deoxynucleotidyl
transferase), CD19+, CD22+
● Anemia
● Neutropenia
● Thrombocytopenia
● The leukocyte count is occasionally very high
(>100•109/L); often is slightly elevated, normal or
decreased
GENERAL CHARACTERISTICS OF CHRONIC
LYMPHOCYTIC LEUKEMIA AND LYMPHOMA (CLL)
● The most common – B-cell form presents with
asymptomatic lymphocytosis in patients with a median
age of 60 years
● The minimum lymphocytosis to make the diagnosis of
CLL is 5•109/L
● The incidence is over 10 per 100,000 per year for persons
over 70 but less than 1/100,000 for those under 50
● More common in males and in whites
● The peripheral blood contains fragile lymphocytes which
are frequently disrupted in the process of making the
smear, producing the so–called smudge cells (KleinGumprecht bodies)
PERIPHERAL BLOOD FINDINGS IN
CHRONIC LYMPHOCYTIC LEUKEMIA
● Leukocytosis due to lymphocytes that
exceed 5•109/L
● Moderate anemia
● The presence of smudge cells in the
blood smear
GENERAL CHARACTERISTICS OF
MYELOID NEOPLASMS
● Originate from a progenitor cell that
normally gives rise to terminally
differentiated cells of the myeloid series
(erythrocytes, granulocytes, monocytes, and
platelets)
● The disease almost always involves bone
marrow and to a lesser degree the
secondary hematopoietic organs (spleen,
liver, and lymph nodes)
PERIPHERAL BLOOD FINDINGS IN ACUTE
MYELOGENOUS LEUKEMIA
● At least 20% myeloid blasts in blood (and/or in bone
marrow)
● Anemia
● “Hiatus leukemicus” (presence of myeloblasts and
promyelocytes, but absence of myelocytes and
metamyelocytes)
● Thrombocytopenia
● The number of leukemic cells in the peripheral blood is
highly variable, sometimes being more 100•109/L, but
being under 10•109/L in about 50% of the patients
● Occasionally the peripheral blood smear may not contain
any blasts (aleukemic leukemia)
GENERAL CHARACTERISTICS OF CHRONIC
MYELOGENOUS LEUKEMIA (CML)
● Refers to chronic myeloproliferative
disorders
● CML affects primarily adults, peaking in
incidence between ages 30 and 40 years
● The diagnosis of CML is established by
identifying a clonal expansion of
hematopoietic stem cell possessing a
reciprocal translocation between
chromosomes 9 and 22
● The disease is characterized by inevitable
transition from a chronic phase to an
accelerated phase and on to blast crisis
FORMATION OF CHIMERIC ONCOGENE IN CHRONIC
MYELOGENOUS LEUKEMIA
CHRONIC
MYELOGENOUS
LEUKEMIA
9
NORMAL
CHROMOSOMES
9
22
22
bcr
locus
bcr
locus
abl
oncogene
abl
oncogene
abl-bcr
hybrid
gene
Tyrosine
kinase
PERIPHERAL BLOOD FINDINGS IN
POLYCYTHEMIA VERA
● The erythrocytes number 6 to 12·109/L, the
Hb is 180 to 240 g/L
● Polychromatic cells and normoblasts may
be found
● Thrombocytosis (in ~2/3 of patients), often >
1000·109/L; functional platelet abnormalities
(e.g. decreased aggregation in response to epinephrine)
● Moderate neutrophilia in the range of 10 to
30·109/L; immature granulocytes in ~50% of
cases
● Basophils are often absolutely increased