HLA CLASS II ANTIGENS AND HAPLOTYPES ASSOCIATED WITH SUSCEPTIBILITY OF LEUKEMIAS AND MYELODYSPLASTIC SYNDROME

Vojvodic S., and D. Ademovic-Sazdanic (2011): HLA class II antigens and haplotypes associated with susceptibility of leukemias and myelodysplastic syndrome. - Genetika, Vol 43, No. 2, 361- 370. Genetical and environmental factors play an interactive role in the development of acute and chronic leukemias. HLA antigens have been considered as possible genetic risk factors. The aim of this work was to investigate a possible association between HLA class II polymorphisms and leukemias and myelodysplastic syndrome. In the present study we investigated HLA class II antigens,DR/DQ and DR51/DR52/DR53 haplotypes in 100 patients: 7 suffering from myelodysplastic syndrome (MDS), 37 from acute lymphoblastic leukemia(ALL), 32 from acute myeloid leukemia (AML) and 24 from chronic myeloid leukemia(CML). A panel of 210 healthy unrelated individuals of the same origin, from Vojvodina, served as controls.HLA phenotyping was performed by two color fluorescence method. In patients suffering from MDS was found a positive association with DR7(RR=2.598, EF=0.175) and DQ7(3)(RR=4.419, EF=0.632), while negative association was found for DR15(2)(RR=0.405, PF=0.172) and DQ6(1) (RR=0.889, PF=0,936). Positive association was found in the group of patients with ALL for DR7(RR=2.391, EF=0.688) and DQ2(RR=1.62, EF=0.15), while negative association was found with DQ5(1)(RR=0.075, PF=0.324). In the group of patients with AML, there were positive associations with DR11(5)(RR=1.732, EF=0.211), DQ2(RR=1.594, EF=0.151) and DQ7(3) (RR=2.547, EF=0.266), while possible protective antigen was DQ5(1) (RR=0.107, RF=0.701). Higher RR than 1 and EF>0.15, in patients suffering from CML was found for DQ6(1)(RR=1.661,EF=0.232), while negative association was found for DR4 (RR=0.182,PF=0.155). Possible protective haplotype in this study was DR3DQ8(3) for patients suffering from AML(RR=0.007, PF=0.501). The distribution of DR53-DR53 haplotypes showed significant difference in male patients with ALL(6% vs 0.09%), while DR52-DR52 haplotype was significantly less frequent in male patients with CML (4% vs 20.47%) and female patients with MDS (1% vs 18.57%), respectively, in comparison to controls. We deduced that DR7 antigen in male patients with ALL has the greatest impact to the higher frequency of DR53-DR53 haplotype in this type of leukemia. The role of HLA antigens as risk factors for development of leukemias in our population was shown and furthermore it could be useful in clinical practice.