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Blood group change in acute myeloid leukemia
Rakul K. Nambiar, MD, Geetha Narayanan, MD, DM, N. P. Prakash, DM, and K. Vijayalakshmi, MD
Blood group antigens are either sugars or proteins found attached to
the red blood cell membrane. ABO blood group antigens are the most
clinically important antigens because they are the most immunogenic.
As red blood cell antigens are inherited traits, they are usually not altered
throughout the life of an individual. There have been occasional case
reports of ABO blood group antigen change in malignant conditions. We
report two such cases of ABO antigen alteration associated with acute
myeloid leukemia. These patients had suppression of their blood group
antigens during their leukemic phase, and the antigens were reexpressed
when the patients attained remission.
R
ed blood cell (RBC) antigens are inherited traits and,
as such, their expression is constant throughout the life
of an individual. RBC antigen change has been occasionally described in association with hematological malignancies. These modifications of blood group antigens
usually revert to normal after remission is attained. We report
two cases of patients with acute myeloid leukemia (AML) who
had ABO antigen alteration during the acute leukemic phase
and reexpression of their original ABO antigen upon remission.
CASE DESCRIPTIONS
Two patients diagnosed with AML M5 (based on the
French-American-British classification) had discrepancy in
their detected blood group by forward cross-matching; their
clinical and laboratory features are summarized in the Table.
Reverse cross-matching was done in the first case, which failed to
show the presence of anti-B antibodies. Reverse cross-matching
revealed the presence of only anti-A antibodies. Elution and
adsorption studies were performed. The patient’s red cells were
incubated with anti-B sera, followed by elution of adsorbed
anti-B on her cells. The elute was then tested with group B
and group O red cells for the presence of anti-B antibodies.
The elute showed positive results with B red cells but a negative
reaction with group O red cells, thus confirming the presence
of B antigen on the patient’s RBC. The patient was started on
7 + 3 induction with cytarabine and daunorubicin, followed
by consolidation with high-dose cytarabine. The strength of
reaction of the patient’s RBC with anti-B antibodies increased
progressively with treatment. By the end of the second con74
Table. Clinical and laboratory features of our cases
Features
Case 1
Case 2
Age (years)
29
14
Gender
Female
Male
Diagnosis
AML M5 (FAB)
AML M5 (FAB)
Cytogenetics
46 XX
50% 46 XY, 50% 45 XY
Flow cytometry
CD13, CD33, CD64,
D117, anti-MPO, CD11c,
CD34, HLA-DR positive
CD13, CD33, CD64,
D117, anti-MPO, CD11c,
CD34, HLA-DR positive
Induction
chemotherapy
7+3
7+3
Consolidation
3 × high-dose cytarabine
3 × high-dose cytarabine
Original blood
group
B
A
Detected blood
group
O
O
Regained original
blood group
After second
consolidation
After second
consolidation
AML indicates acute myeloid leukemia; FAB, French-American-British classification
system; HLA-DR, human leukocyte antigen—antigen D related.
solidation, there was strong reaction with anti-B antibodies,
and she regained her original blood group (B group). Thus, the
original blood group B antigen was suppressed during the leukemic phase, and upon remission B antigens were reexpressed.
Similarly in the second case, the original blood group B antigen
was suppressed during the leukemic phase, and B antigens were
reexpressed upon remission.
DISCUSSION
Loss or diminished expression of RBC antigens has been
reported in both solid and hematological malignancies. ABO
blood group antigen is the most commonly altered blood group
antigen (1–4). For hematopoietic diseases, the loss of expression
From Regional Cancer Centre, Trivandrum, India.
Corresponding author: Geetha Narayanan, MD, DM, Professor and Head,
Department of Medical Oncology, Regional Cancer Centre, Trivandrum 695011,
India (e-mail: [email protected]).
Proc (Bayl Univ Med Cent) 2017;30(1):74–75
results predominantly from a mutation affecting antigen production in the stem cell. Complete or partial loss of antigen
expression is seen among the progenitors of RBC arising from
this affected stem cell, whereas the RBCs arising from unaffected
stem cells usually express normal RBC antigens. Loss or weakening of ABO antigens is usually detected as a discrepancy in
the forward and reverse typing of patients. ABO antigens are the
most frequently reported blood group antigen alteration because
they are routinely tested for all patients before transfusion.
A, B, and H antigens are formed from the same precursor
substance. The production of ABO antigens depends on the
functioning of two glycosyl transferases. The first enzyme, H
transferase, adds L-fucose to the terminal galactose of the precursor substance. The H substance is then acted on by the A or
B transferases that add an N-acetyl galactosamine or a galactose,
respectively. There are two possible mechanisms for the weakening of ABO antigens in hematopoietic diseases. The first mechanism is the inactivation of A/B transferases, and the second is the
inactivation of H transferase. In the first mechanism (5–8), there
is decreased expression of the A and B antigens with a concurrent increase in H antigen. The H antigen is not converted to
A and B antigen due to the inactivation of the A/B transferases.
A and B transferase genes are encoded on chromosome 9, and
they may be inactivated as a 9;22 chromosomal translocation.
This is the plausible explanation for ABO alteration in CML.
The second suggested mechanism for the loss of ABO antigens
is inactivation of the H transferase encoded at 19q13 (9, 10). H
transferase inactivation would result in decreased H substance
and a resulting decrease in A and/or B substance.
ABO antigen alterations are more commonly seen in AML,
although a translocation involving chromosome 9 is seldom seen
in AML. In a study of 12 AML patients with weakening of the
ABO antigens, it was noted that ABO gene inactivation was not
random (11). In 4 of 12 patients studied, only the maternally
derived A or B gene was noted to be affected, suggesting a possibility of genomic imprinting.
Loss and weakening of ABO antigens has also been reported
prior to the diagnosis of an underlying hematopoietic malig-
January 2017
nancy. This is usually noted in the setting of myelodysplasia,
where a patient with longstanding myelodysplasia has a blood
group alteration and later manifests with AML (12, 13). Thus,
any loss of ABO antigens should culminate in the search for
an underlying hematopoietic malignancy. Variations in ABO
antigens may also reflect the status of the malignancy. Upon
remission, there is return of the original blood group, and with
recurrence, there is suppression of blood group antigens (14).
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