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INTERNATIONAL CONGRESS OF

CancerGenetics

• Distribution of HLA Class I and II Alleles in Iranian patients with Myeloid leukemias: Insights into Genetic Predisposition

• Fatemeh Mirzaei,^1,* kurush kalantar ,² Andishe mosafa ,³
  1. Shiraz university of medical immunology
  2. Shiraz university of medical sciences
  3. Shiraz university of medical immunology
  
  
  
• Introduction: Chronic myeloid leukemia (CML) and acute myeloid leukemia (AML) are hematological malignancies originating from myeloid progenitor cells, characterized by clonal proliferation and impaired differentiation. Globally, CML accounts for less than 0.5% of cancers and 15% of adult leukemias, while AML represents approximately 1% of cancers and 30-35% of adult leukemias. Both leukemias exhibit distinct demographic patterns in Iran, with CML patients diagnosed at younger ages compared to global averages. Genetic abnormalities, including chromosomal translocations and somatic mutations, significantly influence leukemia pathogenesis. Notably, immune-related genetic factors, especially human leukocyte antigen (HLA) polymorphisms located on chromosome 6, have emerged as potential contributors to leukemia susceptibility. Previous international studies identified various HLA alleles associated with leukemia risks, yet data specific to Iranian populations remain limited, particularly regarding HLA class I (HLA-A, HLA-B) and class II (HLA-DR) alleles. This study aims to investigate the distribution and potential immunogenetic associations of HLA alleles among Iranian CML and AML patients
• Methods: This case-control study involved two independent cohorts, including 54 patients with CML (324 age- and sex-matched healthy controls) and 155 patients with AML (938 matched controls), recruited from oncology and hematology clinics at Shahid Motahari Hospital, Shiraz University of Medical Sciences, Iran. Diagnoses adhered to WHO criteria, confirming CML through cytogenetic and molecular identification of the Philadelphia chromosome t(9;22) and/or BCR-ABL1 gene fusion. AML diagnosis required a bone marrow blast count exceeding 20%, supported by morphological, immunophenotypic, cytogenetic, and molecular tests. Genomic DNA was isolated from peripheral blood leukocytes using the SinaClon DNA Blood Mini Kit. Low-resolution HLA typing of the HLA-A, HLA-B, and HLA-DRB1 loci was performed via polymerase chain reaction with sequence-specific primers (PCR-SSP). Allele frequencies between patients and controls were compared using chi-square tests, with odds ratios (ORs) and 95% confidence intervals (CIs) calculated to assess disease susceptibility.
• Results: In CML patients, the HLA-B38 allele was significantly more frequent (16.7%) compared to controls (7.7%, p=0.03), presenting an OR of 2.39 (95% CI: 0.81–0.99), suggesting increased susceptibility to CML. No statistically significant associations were identified for AML patients after correcting for multiple comparisons. However, trends toward clinical relevance were observed, including a slightly higher frequency of HLA-DRB115 in AML patients (28.7%) versus controls (24.2%, OR=1.263, p=0.095), and a potential protective effect of HLA-DRB104 (14.6% in AML versus 18.8% in controls, OR=0.743, p=0.083). Rare alleles, such as HLA-B78, displayed high ORs but lacked statistical robustness due to low frequencies and broad confidence intervals. Direct comparisons between AML and CML patients revealed subtle differences but no statistically significant allele frequency deviations, underscoring overlapping yet distinct immunogenetic profiles.
• Conclusion: This study provides crucial insights into HLA allele distribution among Iranian patients with myeloid leukemias. The significant association of HLA-B38 with increased CML risk aligns with international observations highlighting the relevance of class I alleles in leukemia susceptibility. Despite identifying no statistically robust associations for AML, suggestive trends involving HLA-DRB115 and HLA-DRB1*04 support the role of class II alleles in immune surveillance modulation. The immunogenetic distinctions between AML and CML imply disease-specific roles of HLA molecules, with practical implications for personalized immunotherapy and donor selection strategies in hematopoietic stem cell transplantation. Future investigations should incorporate high-resolution HLA typing, larger sample sizes, inclusion of additional immune-related loci (e.g., HLA-C and KIR genes), and integration of somatic mutation data to deepen our understanding of leukemia pathogenesis and genetic predispositions.
• Keywords: CML, HLA-A ,HLA-B ,HLA-DR