Unknown

Dataset Information

0

Donor killer cell Ig-like receptor B haplotypes, recipient HLA-C1, and HLA-C mismatch enhance the clinical benefit of unrelated transplantation for acute myelogenous leukemia.


ABSTRACT: Killer cell Ig-like receptors (KIRs) interact with HLA class I ligands to regulate NK cell development and function. These interactions affect the outcome of unrelated donor hematopoietic cell transplantation (HCT). We have shown previously that donors with KIR B versus KIR A haplotypes improve the clinical outcome for patients with acute myelogenous leukemia by reducing the incidence of leukemic relapse and improving leukemia-free survival (LFS). Both centromeric and telomeric KIR B genes contribute to the effect, but the centromeric genes are dominant. They include the genes encoding inhibitory KIRs that are specific for the C1 and C2 epitopes of HLA-C. We used an expanded cohort of 1532 T cell-replete transplants to examine the interaction between donor KIR B genes and recipient class I HLA KIR ligands. The relapse protection associated with donor KIR B is enhanced in recipients who have one or two C1-bearing HLA-C allotypes, compared with C2 homozygous recipients, with no effect due to donor HLA. The protective interaction between donors with two or more, versus none or one, KIR B motifs and recipient C1 was specific to transplants with class I mismatch at HLA-C (RR of leukemia-free survival, 0.57 [0.40-0.79]; p = 0.001) irrespective of the KIR ligand mismatch status of the transplant. The survival advantage and relapse protection in C1/x recipients compared with C2/C2 recipients was similar irrespective of the particular donor KIR B genes. Understanding the interactions between donor KIR and recipient HLA class I can be used to inform donor selection to improve outcome of unrelated donor hematopoietic cell transplantation for acute myelogenous leukemia.

SUBMITTER: Cooley S 

PROVIDER: S-EPMC4031316 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature

altmetric image

Publications

Donor killer cell Ig-like receptor B haplotypes, recipient HLA-C1, and HLA-C mismatch enhance the clinical benefit of unrelated transplantation for acute myelogenous leukemia.

Cooley Sarah S   Weisdorf Daniel J DJ   Guethlein Lisbeth A LA   Klein John P JP   Wang Tao T   Marsh Steven G E SG   Spellman Stephen S   Haagenson Michael D MD   Saeturn Koy K   Ladner Martha M   Trachtenberg Elizabeth E   Parham Peter P   Miller Jeffrey S JS  

Journal of immunology (Baltimore, Md. : 1950) 20140418 10


Killer cell Ig-like receptors (KIRs) interact with HLA class I ligands to regulate NK cell development and function. These interactions affect the outcome of unrelated donor hematopoietic cell transplantation (HCT). We have shown previously that donors with KIR B versus KIR A haplotypes improve the clinical outcome for patients with acute myelogenous leukemia by reducing the incidence of leukemic relapse and improving leukemia-free survival (LFS). Both centromeric and telomeric KIR B genes contr  ...[more]

Similar Datasets

| S-EPMC2628378 | biostudies-literature
| S-EPMC7988214 | biostudies-literature
| S-EPMC5029895 | biostudies-literature
| S-EPMC6056273 | biostudies-literature
| S-EPMC7002238 | biostudies-literature
| S-EPMC5198579 | biostudies-literature
| S-EPMC1937576 | biostudies-literature
| S-EPMC3124317 | biostudies-literature
| S-EPMC2832209 | biostudies-literature
| S-EPMC7365916 | biostudies-literature