Association of inhibitory KIR-HLA class I interactions with different types of leukemia

Interactions between inhibitory polymorphic killer-cell immunoglobulin-like receptors (KIRs) and their HLA class I ligands control the killing capacity of NK cells. We previously showed that the frequency of specific inhibitory KIR genes with their HLA class I ligands was increased in different forms of leukemia compared to healthy volunteers. To confirm this finding and to correct for multiple comparisons of the first study, we reanalyzed the frequency of these specific inhibitory KIR-HLA genes in a larger and homogenous cohort of leukemic patients. We included the KIR and HLA class I genotypes of 48 B-CLL, 29 B-ALL, 39 CML and 49 AML patients and compared them with a larger control group of 187
unrelated, healthy ethnic-matched individuals. The results obtained in this extended study correlated with most of the previously defined inhibitory KIR-HLA class I interactions in the different leukemic groups. More specific, the frequency of KIR3DL1 homozygotes that were positive for HLA-Bw4 was still strongly associated with B-CLL patients in comparison to healthy volunteers (52.1% vs. 29.4%, respectively). Because it has been shown that the cell surface expression and the strength of inhibition varies among different KIR3DL1 allotypes, we also considered the allelic polymorphism of the KIR3DL1 gene in these B-CLL patients. The most common KIR3DL1 alleles found in the B-CLL patients (n¼42) were KIR3DL1*001 (21.4%), 3DL1*005 (16.6%), 3DL1*004 (15.4%) and 3DL1*002 (14.3%). By contrast, the KIR3DL1*015, which is the dominant KIR3DL1 allotype in Africans, was rare (2.4%)in these leukemic patients. Furthermore, the majority of B-CLL patients (66.7%) had at least one copy of a high-expression
KIR3DL1 allele. In conclusion, our study found an increased number of inhibitoryKIR-HLAinteractions in different groups of leukemia that can influence the NK cell activity.