P106 Killer immunoglobilun-like receptors (KIR) BB haplotype confers susceptibility to acute childhood lymphoblastic leukemia (ALL) and 2DS2, 2DS3 and 2DS4 activating genes are of low risk in mexican children

Abstract

Aim NK cells have the ability to destroy leukemic cells when lacking the ligand for the corresponding inhibitory KIRs. It is documented, that a strong GVHD effect mediated by alloreactive NK cells, results in a reduced risk for relapse in acute myeloid leukemia, and it depends of the inhibitory and stimulatory signals mediated through their KIR ligands. We looked for KIR gene frequencies and haplotypes in ALL Mexican Mestizo children. Methods KIR and HLA genotyping was performed in 66 ALL patients and 357 controls, all of them, Mexican Mestizos. The presence of 14 KIR genes was detected using a PCR-SSP technique with four multiplex reactions. HLA typing was done using a Luminex PCR-SSOP method. Frequency (%) for KIR genes was determined by direct counting. Genotypes were assigned according to www.allelefrequencies.net. A and B haplotypes were deduced from the genotype data. The gene content and haplotype frequencies were compared between patients and controls, using the Chi 2 test with the SPSS17 software. Results We found a significant decrease of 2DS4 (54.5% vs. 72.8%; OR = 0.45; CI = 0.26–0.77; p = 0.003), 2DL2 (21.2% vs. 42.9%; OR = 0.36; CI = 0.19–0.67; p = 0.001), 2DS2 (19.7% vs. 44.8%; OR = 0.302; CI = 0.16–0.57; p p = 0.001) in ALL children. Framework genes were present in all individuals (2DL4, 3DL2 and 3DL3). The frequency of AA genotype was significantly decreased in the cases vs. controls (31.9% vs. 45.5%; OR = 0.56; CI = 0.33–0.96; p = 0.03). Conclusions A low risk was shown for ALL, if carrying 2DS4, 2DL2, 2DS2 or 2DS3 in Mexicans. We also found that the AA haplotype is protective and contains the 2DS4 activating gene. Controversial results exist in ALL depending on ethnicity. In Canadians, a reduced risk exists when activating KIR genes are present, while in Germans no association was shown; AA was not associated in non-hispanics, while an increased risk was observed in Hispanics. Thus, it is crucial to analyze specific ethnic groups, since Hispanics include many different racial backgrounds. In our study, which is the first one done in Mexicans with ALL, only Mestizos were included. Our results are consistent with data demonstrating that KIR genes play an important role in disease survival. Therefore, more studies of KIR genes and ALL must be done in non-Caucasians.