KIR2DS3 is Associated with Protection against Acute Myeloid Leukemia

Abstract

<b>Background</b>: 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. <br/><b>Objective</b>: The aim of this study was to investigate the impact of compound KIR-HLA genotype on susceptibility to acute leukemia. <br/><b>Methods</b>: 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. <br/><b>Results</b>: 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 co-inheritance 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 inhibi-tory combinations was the main feature in this group. <br/><b>Conclusion</b>: Our findings may suggest a mechanism for escape of leukemic cells from NK cell immunity.