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


Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • de Smith, AJ; Walsh, KM; Ladner, MB; Zhang, S; Xiao, C; Cohen, F; Moore, TB; Chokkalingam, AP; Metayer, C; Buffler, PA; Trachtenberg, EA; Wiemels, JL

Published Date

  • April 17, 2014

Published In

Volume / Issue

  • 123 / 16

Start / End Page

  • 2497 - 2503

PubMed ID

  • 24518758

Pubmed Central ID

  • 24518758

Electronic International Standard Serial Number (EISSN)

  • 1528-0020

Digital Object Identifier (DOI)

  • 10.1182/blood-2013-11-540625


  • eng

Conference Location

  • United States