KIR2DS3 is associated with protection against acute myeloid leukemia

Background: Interaction between killer cell immunoglobulin-like receptors (KIR) and human leukocyte antigen (HLA) class I molecules is important for regulation of natural killer (NK) cell function. Objective: The aim of this study was to investigate the impact of compound KIR-HLA genotype on susceptibility to acute leukemia. Methods: Cohorts of Iranian patients with acute myeloid leukemia (AML; n=40) and acute lymphoid leukemia (ALL; n=38) were genotyped for seventeen KIR genes and their three major HLA class I ligand groups (C1, C2, Bw4) by a combined polymerase chain reaction-sequence-specific primers (PCR-SSP) assay. The results were compared with those of 200 healthy control individuals. Results: We found a significantly decreased frequency of KIR2DS3 in AML patients compared to control group (12.5 vs. 38, odds ratio=0.23, p=0.0018). Also, the KIR3DS1 was less common in AML group than controls (27.5 vs. 44.5, p=0.0465, not significant after correction). Other analyses including KIR genotypes, distribution and balance of inhibitory and activating KIR+HLA combinations, and coinheritance of activating KIR genes with inhibitory KIR+HLA pairs were not significantly different between leukemia patients and the control group. However, in AML patients a trend toward less activating and more inhibitory KIR-HLA state was observed. Interestingly, this situation was not found in ALL patients and inhibition enhancement through increase of HLA ligands and inhibitory combinations was the main feature in this group. Conclusion: Our findings may suggest a mechanism for escape of leukemic cells from NK cell immunity