Acute myeloid leukemia is a disease associated with HLA-C3

We aimed to observe human leukocyte antigen (HLA) associations with human acute myeloid leukemia (AML) in a large population, in order to investigate the roles of HLA in leukemogenesis. Furthermore, we examined the HLA association according to morphological, cytogenetic, immunological, and clinical classifications.

We performed HLA genotyping, bone marrow studies, cytogenetic analyses, and fluorescence-activated cell sorting analyses. A clinical outcome database was constructed, and the HLA frequency, gene frequency, relative risk (RR), linkage disequilibrium, and the 2-locus and 3-locus haplotype frequency using the Mattiuz formula were calculated. For the healthy controls, Korean HLA data published by Park and co-workers were used.

AML was found to be associated with HLA-C3 (RR = 1.46; p < 0.001). In the French-American-British (FAB) classification, acute myelomonocytic leukemia (AML-M4) was associated with HLA-C3 (47.2 vs. 74.1%; RR = 3.13; p = 0.005), in cytogenetic classification, del(9), which is frequently observed in AML-M4, was also associated with HLA-C3 (47.2 vs. 100%; RR = 13.43; p = 0.024), and in clinical classification, incomplete remission was associated with HLA-C3 as well (47.2 vs. 63.2%; RR = 1.92; p = 0.002). No correlations between AML and immunological classifications were observed. Moreover, and in terms of 2-locus haplotypes, AML was found to be associated with HLA-C3/B62 (HLA-C3 gene frequency 0.3415; HLA-B62 gene frequency 0.1361; linkage disequilibrium 0.0136; haplotype frequency 4.15 vs. 6.0%; p < 0.05). In clinical classification, incomplete remission (linkage disequilibrium 0.0136; haplotype frequency 4.15 vs. 13.6%; p = 0.013) and relapse (linkage disequilibrium 0.0136; haplotype frequency 4.15 vs. 71.0%; p = 0.044) were associated with HLA-C3/B62, whereas no association was observed for FAB, cytogenetic and immunological classifications. No association was observed for the 3-locus haplotype.

The HLA-C3 antigen and the 2-locus haplotype are associated with AML.