Abstract
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.
Red 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 consolidation, 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.
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.
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 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 malignancy. 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).
References
- 1.Kolins J, Holland PV, McGinniss MH. Multiple red cell antigen loss in acute granulocytic leukemia. Cancer. 1978;42(5):2248–2253. doi: 10.1002/1097-0142(197811)42:5<2248::aid-cncr2820420524>3.0.co;2-t. [DOI] [PubMed] [Google Scholar]
- 2.Satheesh P, Thomas M, Rajan GB. Change in the ABO blood group phenotype. J Assoc Physicians India. 1994;42(10):830. [PubMed] [Google Scholar]
- 3.Chiewsilp P, Atichartakarn V. Change of red cell B antigen in a leukemic patient. J Med Assoc Thai. 1981;64(8):413–417. [PubMed] [Google Scholar]
- 4.Yamada K, Yoshizaki Y, Fujii Y, Inoue M, Ishida Y, Shinohara K, Kaneko T, Hiroshige Y, Matsumoto N. Concurrent ABO blood type change and erythrophagocytosis by leukemic cells in a case of acute myeloblastic leukemia. Nihon Ketsueki Gakkai Zasshi. 1985;48(6):1409–1413. [PubMed] [Google Scholar]
- 5.van der Hart M, van der Veer M, van Loghem JJ. Change of blood group B in a case of leukemia. Vox Sang. 1962;7:449–453. doi: 10.1111/j.1423-0410.1962.tb03276.x. [DOI] [PubMed] [Google Scholar]
- 6.Hoogstraten B, Rosenfield RE, Wasserman LR. Change of ABO blood type in a patient with leukemia. Transfusion. 1961;1(1):32–35. doi: 10.1111/j.1537-2995.1961.tb00008.x. [DOI] [PubMed] [Google Scholar]
- 7.Crookston MC. Anomalous ABO, H, Ii phenotypes in disease. In: Garratty G, editor. Blood Group Antigens and Disease. Arlington, VA: American Association of Blood Banks; 1983. pp. 67–84. [Google Scholar]
- 8.Yoshida A, Kumazaki T, Dave V, Blank J, Dzik WH. Suppressed expression of blood group B antigen and blood group galactosyltransferase in a preleukemic subject. Blood. 1985;66(4):990–992. [PubMed] [Google Scholar]
- 9.Reid ME, Bird GW. Associations between human red cell blood group antigens and disease. Transfus Med Rev. 1990;4(1):47–55. doi: 10.1016/s0887-7963(90)70247-7. [DOI] [PubMed] [Google Scholar]
- 10.Kuhns WJ, Oliver RT, Watkins WM, Greenwell P. Leukemia-induced alterations of serum glycosyltransferase enzymes. Cancer Res. 1980;40(2):268–275. [PubMed] [Google Scholar]
- 11.Dobrovic A, O'Keefe D, Sage RE, Batchelder E. Imprinting and loss of ABO antigens in leukemia. Blood. 1993;82(5):1684–1685. [PubMed] [Google Scholar]
- 12.Salmon C. Blood groups changes in preleukemic states. Nouv Rev Fr Hematol Blood Cells. 1976;17(1–2):211–220. doi: 10.1007/978-3-642-66312-3_14. [DOI] [PubMed] [Google Scholar]
- 13.Lopez M, Bonnet-Gajdos M, Reviron M, Janvier D, Huet M, Salmon C. An acute leukaemia augured before clinical signs by blood group antigen abnormalities and low levels of A and H blood group transferase activities in erythrocytes. Br J Haematol. 1986;63(3):535–539. doi: 10.1111/j.1365-2141.1986.tb07531.x. [DOI] [PubMed] [Google Scholar]
- 14.Gold ER, Tovey GH, Benney WE, Lewis FJW. Changes in group A antigen in a case of leukaemia. Nature. 1959;183(4665):892–893. doi: 10.1038/183892a0. [DOI] [PubMed] [Google Scholar]