CERTAIN HLA ANTIGENS ARE ASSOCIATED WITH SPECIFIC MORPHOLOGIC AND CYTOGENETIC SUBSETS OF ACUTE MYELOID-LEUKEMIA

Although many associations have been found between specific HLA antige ns and an increased susceptibility to various diseases, previous attem pts to associate class I and II antigens with acute myeloid leukemia ( AML) have been inconclusive, probably due in part to the heterogeneity of AML. We subdivided 165 consecutive adults with AML de novo into di stinct clinical, morphological, and cytogenetic subsets and then teste d for statistically significant associations with specific HLA antigen s. Both morphology and cytogenetic pattern identified subsets of patie nts with important clinical features and different outcomes. Ten stati stically significant (P < 0.05) HLA cytogenetic associations were obse rved: HLA-A11 with t(8;21), A26 with t(15;17), B7 with 11q23 abnormali ties, B44 with +8, Cw2 with -20/del(20q), DR3 with t(15;17) and FAB-MB , DR4 with inv(16) and FAB-M4Eo, DQ2 with +8, and DQ6 with +22. HLA-DQ 1 had a negative association with -5/del(5q), which was present in 13% of the 165 AML patients overall but in none of the 27 with DQ1. Certa in HLA antigens were significantly correlated with more favorable remi ssion rates, remission duration and survival. Possible mechanisms for the association of HLA antigens with particular subtypes of AML includ e the linkage or co-inheritance of an oncogene, the facilitation of bi nding of a transforming virus, toxin, or cytokine, or a permissive rol e involving impaired immune recognition of an emerging neoplasm. Given the heterogeneity of both the HLA system of immune recognition genes and the cytogenetic subtypes of AML, however, larger numbers of patien ts must be studied to have confidence that biologically important rela tionships truly exist.