Killer-cell immunoglobulin-like receptors (KIRs) that regulate natural-killer cells are highly polymorphic. Some KIR2DL1 alleles encode receptors that have stronger signaling function than do others receptors. We tested the hypothesis that the clinical outcomes of patients receiving allogeneic hematopoietic stem-cell transplantation (HSCT) could be affected by donor KIR2DL1 polymorphism. We found that patients who received a donor graft containing the functionally stronger KIR2DL1 allele with arginine at amino acid position 245 (KIR2DL1-R245) had better survival and lower cumulative incidence of disease progression than those patients who received a donor graft that contained only the functionally weaker KIR2DL1 allele with cysteine at the same position (KIR2DL1-C245). The effect of KIR2DL1 allelic polymorphism was similar in patients with acute myeloid leukemia or acute lymphoblastic leukemia among all allele groups. Patients who received a KIR2DL1-R245–positive graft with HLA-C receptor-ligand mismatch had better survival and lower risk of leukemia progression than those who received a KIR2DL1-C245 homozygous graft. Thus, donor KIR2DL1 allelic polymorphism affects recipient outcomes after allogeneic HSCT. These findings have substantial implications for prognostication and donor selection.
Bari R, Rujkijyanont P, Sullivan E, Kang G, Turner V, Gan K, Leung W. Effect of donor KIR2DL1 allelic polymorphism on the outcome of pediatric allogeneic hematopoietic stem cell transplantation. Journal of Clinical Oncology 31(30): 3782-3790, 2013. PMID: 24043749 PMCID: PMC3795888.