HLA-B∗, C∗, DRB1∗ AND DQB1∗ alleles contribute to susceptibility to acute myeloblastic leukemia in Mexican Mestizo adult patients

Abstract

In Mexicans, (Acute myeloid leukemia) AML comprises 15% of all AL cases. (1/100,000). The contribution of MHC markers to its expression has been suggested. Copy neural loss of heterozygosity for all parts of one haplotype, or somatic mutations in the nucleotide sequences of common A∗ or B∗ alleles, was shown. A∗03, B∗35 was reported in Turkish patients and B∗40 in a small group of Mexicans. We looked for the HLA MHC I & II pattern to unravel the genetic HLA background of AML. We included 282 high risk AML young patients, classified according to their chromosomal rearrangements, undergoing HSC transplantation & 348–708 healthy controls (C). All of them were Mexican Mestizos. Typing was done for: HLA-A∗ P = 70; C = 139; B∗ P = 94 vs. C = 105; C∗; P = 63 vs. C = 106); DRB1∗ (P = 105 vs. C = 299); and DQB1∗ (P = 354) loci, that were typed by PCR-SSOP/SBT. AF, Chi2, p & ORs were calculated with the SPSS17 software. Estimated Haplotypes Frequency was done (Arlequin software). We found associated in AML: B∗44:03(OR = 5.73); C∗16:01 (OR = 3.40); DRB1∗01:03 (OR = 6.39); DQB1∗02:02 (OR = 2.47); QB1∗05:01 (OR = 1.65); DQB1∗06:03 (OR = 2.08). One protective allele was shown: DQB1∗03:01 (OR = 0.51). DRB1∗07 was not found associated, suggesting that susceptibility is linked to the DQ2 and to the B∗44:03-C∗16:01 haplotype. Two haplotypes involving A∗02:01 were significantly increased in the patients. particularly A∗02-B∗07:02-DRB1∗15-DQB1∗06:02 (1.55 %) & A∗02-B∗39:05-DRB1∗04:07-DQB1∗03:02(1.55%); the prevalent aplotypes in C were: A∗02:01-B∗35:12-DRB1∗08:02-DQB1∗04:02 & A∗02:06-B∗35:01-DRB1∗04-DQB1∗03:02(1.5%). A recent meta-analysis of differential gene expression in AML, found that only 9.6% of the reported genes were replicated in more than one study. They identified 5 major clusters of prognostic genes, none of them involving HLA. A complex genetic etiology is clear suggesting that the interaction of specific amino acids in the HLA groove with different infectious agents and environmental factors, are related to AML expression. Epidemiological studies in Mexico have shown that the incidence of AML is higher in people living in crowded households, having more risk of infections. We provided evidence of HLA association with AML with diverse alleles contribute to the risk, and one involved in protection