HLA-DRB1 Impact on Survival of Induced Leukemic Cells Under ‘Allergic’ Conditions

Background and Objective: Leukaemia is a hematological malignancy of which etiology is still unclear. Like most cancers, many are associated with a genetic defect such as chromosomal translocation. Recent epidemiology studies revealed an inverse relationship between acute lymphoblastic leukemia and allergic rhinitis (AR), a chronic inflammatory condition. This study investigates the impact of HLA-DRB1 alleles on the survival of induced leukemic cells under allergic conditions. Materials and Methods: In this study, a Dermatophagoides pteronyssinus (Der p 1)-sensitized AR subject typed as HLA-DRB1*13 (susceptible allele in AR) and a non-allergic subject with HLA-DRB1*10 (protective allele in AR) of Malay ethnic group were recruited. Peripheral Blood Mononuclear Cells (PBMC) were transfected with the oncogenic MLL/MLLT1 fusion gene to induce leukemia cells. The induced leukaemia-like B cells were co-cultured for five days with Der p1 stimulated PBMC from the same individual. Survival of the B leukemic-like cells was analyzed by flow cytometry. Three experiments were performed, non-parametric statistical analyses: Mann-Whitney for two-group comparisons was used with significance level, p<0.05 Results: Induced leukemic-like cells were CD34lowCD38⁺CD45⁺MLL⁺CD19⁺. This population was significantly reduced in HLA-DRB1*13 samples compared to HLA-DRB1*10 (1.07+0.12% vs 3.53+0.61%, p = 0.05). Significantly decreased regulatory T cells (Tregs) in HLA-DRB1*13 compared to HLA-DRB1*10 (4.93+0.12% vs 6.20+0.17%, p = 0.05) implied increased inflammatory condition. Conclusion: Thus, HLA-DRB1 alleles may be factors that influence the inverse relationship between allergic rhinitis and acute lymphoblastic leukemia. Further studies with a larger sample size are required to confirm the results.