Journal
BLOOD
Volume 124, Issue 14, Pages 2248-2251Publisher
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2014-05-572065
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Funding
- Deutsche Krebshilfe e.V. [110351]
- Forschungskommission of the Medical Faculty of the Heinrich-Heine-Universitat Dusseldorf
- Deutsche Forschungsgemeinschaft [UH 91/7-1]
- British Heart Foundation [PG/09/077/27964] Funding Source: researchfish
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A role for HLA class I polymorphism in childhood acute lymphoblastic leukemia (ALL) has been suggested for many years, but unambiguous associations have not been found. Here, we show that the HLA-C-encoded supertypic epitope C2, which constitutes a high-affinity ligand for the inhibitory natural killer (NK) cell receptor KIR2DL1, is significantly increased in ALL patients (n = 320; P = .005). Stratification for ethnicity and disease subtype revealed a strong association of C2 with B-ALL in German cases (P = .0004). The effect was independent of KIR2DS1 and KIR2DL1 allelic polymorphism and copy number. Analysis of clinical outcome revealed a higher incidence of late relapse (>2.5 years) with increasing number of C2 alleles (P = .014). Our data establish C2 as novel risk factor and homozygosity for C1 as protective for childhood B-ALL supporting a model in which NK cells are involved in immunosurveillance of pediatric B-ALL via interaction of KIR with HLA-C ligands.
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