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.