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J Clin Oncol. 2013 Oct 20;31(30):3782-90. doi: 10.1200/JCO.2012.47.4007. Epub 2013 Sep 16.

Effect of donor KIR2DL1 allelic polymorphism on the outcome of pediatric allogeneic hematopoietic stem-cell transplantation.

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  • 1Rafijul Bari, Piya Rujkijyanont, Erin Sullivan, Guolian Kang, Victoria Turner, Kwan Gan, Wing Leung, St Jude Children's Research Hospital; Wing Leung, University of Tennessee Health Science Center, Memphis, TN.

Abstract

PURPOSE:

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 others. We tested the hypothesis that the clinical outcomes of allogeneic hematopoietic stem-cell transplantation (HSCT) could be affected by donor KIR2DL1 polymorphism.

PATIENTS AND METHODS:

All 313 pediatric patients received allogeneic HSCT at a single institution. Donor KIR2DL1 functional allele typing was retrospectively performed using single nucleotide polymorphism assay.

RESULTS:

Patients who received a donor graft containing the functionally stronger KIR2DL1 allele with arginine at amino acid position 245 (KIR2DL1-R(245)) had better survival (P = .0004) and lower cumulative incidence of disease progression (P = .001) than those patients who received a donor graft that contained only the functionally weaker KIR2DL1 allele with cysteine at the same position (KIR2DL1-C(245)). The effect of KIR2DL1 allelic polymorphism was similar in patients with acute myeloid leukemia or acute lymphoblastic leukemia among all allele groups (P ≥ .71). Patients who received a KIR2DL1-R(245)-positive graft with HLA-C receptor-ligand mismatch had the best survival (P = .00003) and lowest risk of leukemia progression (P = .0005) compared with those who received a KIR2DL1-C(245) homozygous graft.

CONCLUSION:

Donor KIR2DL1 allelic polymorphism affects recipient outcomes after allogeneic HSCT. These findings have substantial implications for prognostication and donor selection.

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PMID:
24043749
[PubMed - indexed for MEDLINE]
PMCID:
PMC3795888
Free PMC Article
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