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

Turganbekova A. Burkitbayev Z. Zhanzakova Z. Baimukasheva D. Saduakas Z. Khamitova D. Abdrakhmanova S. Masalimov Z. Almawi W.Y.
1 March 2026

Human immunology
2026 #87 Issue 3 111680 pp.

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 Fishers 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. Copyright

Acute myeloid leukemia , DPB1 alleles , DQA1 alleles , HLA polymorphisms , Next-generation sequencing

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Scientific and Production Center for Transfusiology, Astana 010000, Kazakhstan; Faculty of Natural Sciences, L.N. Gumilyov Eurasian National University, Astana 010000, Kazakhstan
National Research Oncology Center, Astana, 010000, Kazakhstan
Scientific and Production Center for Transfusiology, Astana, 010000, Kazakhstan
Faculty of Natural Sciences, L.N. Gumilyov Eurasian National University, Astana, 010000, Kazakhstan
School of Medicine, Nazarbayev University, Astana 010000, Kazakhstan; Faculty of Sciences, El-Manar University, Campus at El-Manar, Tunis 2092 Tunisia

Scientific and Production Center for Transfusiology
National Research Oncology Center
Scientific and Production Center for Transfusiology
Faculty of Natural Sciences
School of Medicine

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