Certain HLA antigens are associated with specific morphologic and cytogenetic subsets of acute myeloid leukemia.
Although many associations have been found between specific HLA antigens and an increased susceptibility to various diseases, previous attempts 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 distinct clinical, morphological, and cytogenetic subsets and then tested for statistically significant associations with specific HLA antigens. Both morphology and cytogenetic pattern identified subsets of patients with important clinical features and different outcomes. Ten statistically significant (P < 0.05) HLA cytogenetic associations were observed: HLA-A11 with t(8;21), A26 with t(15;17), B7 with 11q23 abnormalities, B44 with +8, Cw2 with -20/del(20q), DR3 with t(15;17) and FAB-M3, DR4 with inv(16) and FAB-M4Eo, DQ2 with +8, and DQ6 with +22. HLA-DQ1 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. Certain HLA antigens were significantly correlated with more favorable remission rates, remission duration and survival. Possible mechanisms for the association of HLA antigens with particular subtypes of AML include the linkage or co-inheritance of an oncogene, the facilitation of binding of a transforming virus, toxin, or cytokine, or a permissive role 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 patients must be studied to have confidence that biologically important relationships truly exist.
Joventino
L P
LP
Department of Medicine, University of Chicago, IL 60637.
Stock
W
W
Lane
N J
NJ
Daly
K M
KM
Mick
R
R
Le Beau
M M
MM
Larson
R A
RA
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000032:analysis / Q000235:genetics*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002869:Chromosome Aberrations; D018572:Disease-Free Survival; D004351:Drug Resistance; D005260:Female; D020022:Genetic Predisposition to Disease; D006680:HLA Antigens / Q000032:analysis / Q000235:genetics*; D006801:Humans; D007951:Leukemia, Myeloid / Q000145:classification* / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology / Q000401:mortality; D015993:Life Tables; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D012074:Remission Induction; D016019:Survival Analysis; D016896:Treatment Outcome
D000951:Antigens, Neoplasm; D006680:HLA Antigens