Abstract
In the treatment of acute myelogenous leukemia with allogeneic hematopoietic cell transplantation, we previously demonstrated that there is a greater protection from relapse of leukemia when the hematopoietic cell transplantation donor has either the Cen B/B KIR genotype or a genotype having two or more KIR B gene segments. In those earlier analyses, KIR genotyping could only be assessed at the low resolution of gene presence or absence. To give the analysis greater depth, we developed high-resolution KIR sequence-based typing that defines all the KIR alleles and distinguishes the expressed alleles from those that are not expressed. We now describe and analyze high-resolution KIR genotypes for 890 donors of this human transplant cohort. Cen B01 and Cen B02 are the common CenB haplotypes, with Cen B02 having evolved from Cen B01 by deletion of the KIR2DL5, 2DS3/5, 2DP1, and 2DL1 genes. We observed a consistent trend for Cen B02 to provide stronger protection against relapse than Cen B01 This correlation indicates that protection depends on the donor having inhibitory KIR2DL2 and/or activating KIR2DS2, and is enhanced by the donor lacking inhibitory KIR2DL1, 2DL3, and 3DL1. High-resolution KIR typing has allowed us to compare the strength of the interactions between the recipient's HLA class I and the KIR expressed by the donor-derived NK cells and T cells, but no clinically significant interactions were observed. The trend observed between donor Cen B02 and reduced relapse of leukemia points to the value of studying ever larger transplant cohorts.