Study On The Relationship Of Inhibitory KIR Genes And Leukemia

Killer cell immunoglobulin-like receptors(KIRs) are members of the immunoglobulin superfamily expressed on the surface of human NK cells and some T-cell subsets. The natural ligands of KIRs are human leukocyte antigen(HLA) class I molecules which are expressed on most nucleated cells. Upon engagement with HLA class I molecules of target cells, KIRs regulate NK cell function by transmitting inhibitory or activating signals. It was reported that NK cells preferentially kill tumor cells that have capacity to downregulate or lack HLA class I molecules. It was also reported that leukemic cells can reduce expression of HLA class I molecules and might trigger NK cell cytotoxicity. We assume that not only the KIR genes themselves but also their expression might influence the normal function of NK cells, even antileukemic cytotoxic activity. The aim of the present study is to investigate the relationship between the polymorphism and expression level of inhibitory KIR genes and leukemia.To study the polymorphism of inhibitory KIR genes , we developed PCR-SSP methods to detect 8 inhibitory KIR genes. Totally 41 leukemic patients and 46 healthy individuals were analyzed and the expession frequencies of these 8 inhibitory KIR genes were calculated. In comparison, all individuals were KIR2DL4, KIR3DL2 and KIR3DL3 positive, of which the expression frequencies were 100% in both leukemic group and the healthy control group. The expression frequency of KIR2DL2 was significantly higher in the leukemic group than in the healthy control group ( 39.0% vs 19.7%, P<0.05) and there were no significant differences in the expression frequencies of the rest 5 inhibitory KIR genes between patients and controls.To further explore the relationship of the expression levels of inhibitory KIR genes and leukemia, we quantitatively examined the expression levels of KIR2DL1, KIR2DL2, KIR2DL3 genes by competitive PCR in leukemic patients and healthy individuals who were KIR2DL1, KIR2DL2, KIR2DL3 gene positive. It was demonstrated that the expression levels of these three genes were all significantly...