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National Institute of Environmental Health Sciences

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Publication Detail

Title: The role of KIR genes and their cognate HLA class I ligands in childhood acute lymphoblastic leukemia.

Authors: de Smith, Adam J; Walsh, Kyle M; Ladner, Martha B; Zhang, Siming; Xiao, Carmen; Cohen, Franziska; Moore, Theodore B; Chokkalingam, Anand P; Metayer, Catherine; Buffler, Patricia A; Trachtenberg, Elizabeth A; Wiemels, Joseph L

Published In Blood, (2014 Apr 17)

Abstract: Killer cell immunoglobulin-like receptors (KIRs), via interaction with their cognate HLA class I ligands, play a crucial role in the development and activity of natural killer cells. Following recent reports of KIR gene associations in childhood acute lymphoblastic leukemia (ALL), we present a more in-depth investigation of KIR genes and their cognate HLA ligands on childhood ALL risk. Genotyping of 16 KIR genes, along with HLA class I groups C1/C2 and Bw4 supertype ligands, was carried out in 212 childhood ALL cases and 231 healthy controls. Frequencies of KIR genes, KIR haplotypes, and combinations of KIR-HLA ligands were tested for disease association using logistic regression analyses. KIR A/A genotype frequency was significantly increased in cases (33.5%) compared with controls (24.2%) (odds ratio [OR] = 1.57; 95% confidence interval [CI], 1.04-2.39). Stratifying analysis by ethnicity, a significant difference in KIR genotype frequency was demonstrated in Hispanic cases (34.2%) compared with controls (21.9%) (OR = 1.86; 95% CI, 1.05-3.31). Homozygosity for the HLA-Bw4 allele was strongly associated with increased ALL risk exclusively in non-Hispanic white children (OR = 3.93; 95% CI, 1.44-12.64). Our findings suggest a role for KIR genes and their HLA ligands in childhood ALL etiology that may vary among ethnic groups.

PubMed ID: 24518758 Exiting the NIEHS site

MeSH Terms: Case-Control Studies; Child; Child, Preschool; Female; Gene Frequency; Genes, MHC Class I/physiology*; HLA-B Antigens/genetics; Haplotypes; Humans; Ligands; Male; Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics*; Precursor Cell Lymphoblastic Leukemia-Lymphoma/immunology; Receptors, KIR/genetics; Receptors, KIR/physiology*

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