Novel association of HLA-DQA1 and HLA-DPB1 alleles with acute myeloid leukemia susceptibility in (Central Asian) Kazakhstani population: A case-control study.

[BACKGROUND] Acute myeloid leukemia (AML) is a diverse hematological cancer characterized by clonal growth of myeloid precursors in the bone marrow. Although the core genetic pathways involved in AML development are not completely understood, a connection between specific HLA variants and a predisposition to AML, as well as graft-versus-leukemia effects in transplantation, has been observed across various ethnic groups.

[OBJECTIVE] Using high-resolution genotyping, this study investigates the relationship between HLA Class I and Class II alleles and the risk of developing AML in the Kazakhstani population.

[METHODS] The study included 123 patients diagnosed with AML and 350 unrelated healthy controls selected from the national registry of hematopoietic stem cell donors. HLA Class I (HLA-A, -C, -B) and Class II (HLA-DRB1, -DQA1, -DQB1, -DPB1) high-resolution genotyping was conducted using next-generation sequencing. Statistical significance was assessed with chi-square tests (and Fisher's exact tests where suitable).

[RESULTS] Class II alleles showed stronger associations with AML than Class I alleles. At the DQA1 locus, DQA1*05:01:01, DQA1*03:01:01, DQA1*01:01:01, and DQA1*01:02:01 were significantly protective (p < 0.001), while DQA1*04:01:01 was strongly linked to risk (p < 0.001). Protective DPB1 alleles included DPB1*04:01:01 and DPB1*02:01:01, whereas DPB1*01:01:01 increased susceptibility. Among Class I alleles, only HLA-C*02:02:01 was protective, while HLA-B*57:01:01 was associated with a higher AML risk.

[CONCLUSIONS] Class II alleles, especially those within DQA1 and DPB1, are important genetic factors influencing AML susceptibility in the Kazakhstani population.