Loss of red cell A, B, and H antigens is frequent in myeloid malignancies

Abstract

IntroductionThe A, B, and H antigens (hereafter referred to as ABH antigens) are complex carbohydrate structures found on glycoproteins and glycolipids present on the surface of erythrocytes, endothelial cells, and on most epithelial cells. Alleles of the ABO gene code for glycosyltransferases that act on the precursor H antigen. 1,2 In red blood cells, the H antigen is determined by a fucosyltransferase coded for by the FUT1 gene. If the H antigen is absent, there is no substrate for the ABO glycosyltransferases to modify. Homozygous deficiency of FUT1 gives rise to the Bombay phenotype where there are no A or B antigens on the red cell due to lack of the H precursor. The major alleles of the ABO gene are A, which adds N-acetylgalactosamine to give the A antigen; B, which adds galactose to give the B antigen; and O, which is a null allele coding for an inactive transferase incapable of modifying the H antigen. The most frequent of the minor A and B alleles is the A 2 allele, which gives rise to a lower density of A antigen. Weaker alleles such as A 3 and A x show progressively less A antigen. 3 Alteration of ABH antigens in hematologic malignancy was first reported by van Loghem et al, 4 who described very weak A antigen expression on the red cells of a patient with acute myeloid leukemia (AML), who had previously shown normal A antigen expression. Loss of A, B, or H antigens from the surface of red blood cells is now recognized as a recurrent observation in hematologic malignancy. 5,6 In a healthy individual of type A, B, or AB, complete agglutination of the red blood cells is observed after incubation with antibodies reactive against their blood group. In patients with loss of ABH antigens, a varying proportion of red blood cells do not agglutinate, giving a characteristic mixed-field reaction. Mixed-field reactions can also occur in healthy individuals where the reactions are associated with rare alleles of the ABO gene such as A 3 and B 3 .Loss of ABH antigens is also seen in the tumor cells of many types of carcinoma, including bladder, lung, head and neck, cervical, and thyroid, where it has been associated with tumor grade, metastatic potential, and poor prognosis. 7-13 Furthermore, laboratory studies have shown that tumorigenicity is reduced when A or B antigens are expressed. 14,15 Whether the mechanisms of loss of ABH antigens in epithelial tumors and hematologic malignancies are truly analogous to each other remains to be determined.Unlike epithelial malignancies where the loss of ABH antigens is seen in dedifferentiated tumor cells, loss of ABH antigens in myeloid malignancies is only seen on red cells as most hematopoietic cells and precursors do not express ABH antigens. However, malignant stem cells often retain the potential to differentiate along the erythroid lineage. [16][17][18] Thus, loss of ABO expression in the population of red cells derived from a malignant stem cell is an indicator of genetic changes that have occurred in the malignant stem cell. Consistent with this, Salmon et al 19 s...

Mosaicism due to myeloid lineage–restricted loss of heterozygosity as cause of spontaneous Rh phenotype splitting

“…17 Importantly, Rh mosaicism in apparently healthy subjects may have clinically relevant consequences, 18 as already minor proportions of D-positive RBCs in blood units from donors erroneously typed D-negative were demonstrated to incite anti-D immunization in D-negative recipients. 19 Loss of Rh antigens, after ABO, 50 is the second most commonly reported blood group alteration associated with hematologic disease. 15 In this study, one third of the patients suffered from different hematologic diseases, whereas the rest of the study cohort appeared hematologically healthy within even extended observation periods (in comparison, only 1.8% of all patients who receive blood grouping tests at the Division of Blood Group Serology in Vienna suffer from hematologic diseases).…”

Flow Cytofluorometric Analysis in Red Blood Cell Immunology

“…Others have looked at differences in ABH expression on aging RBCs [43], newborn RBCs ( fig. 2) [44], and on RBCs from patients with hematologic malignancies [45,46]. FC has been proposed as a method for routine ABO and D blood typing [35,47].…”

Blood Group Change in Pediatric Leukemia: A Rare Phenomena

“…It has been proposed that in some leukemic patients' epigenetic modification of the promoter of ABO gene in RBCs by leukemic cells leads to its suppression and consequent alteration in the blood group [2]. ABO blood group changes have been more commonly described in AML than in other hematological malignancies [3,4]. However, most of these changes are subtle and detected on molecular studies and not detected on routine blood group typing [3].…”

“…ABO blood group changes have been more commonly described in AML than in other hematological malignancies [3,4]. However, most of these changes are subtle and detected on molecular studies and not detected on routine blood group typing [3]. Blood group changes have been identified prior to the diagnosis of underlying leukemia and also have shown to herald leukemia relapse [5].…”