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Risk of developing chronic lymphocytic leukemia is influenced by HLA-A class I variation

Leukemia volume 27, pages 255–258 (2013)Cite this article

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Although chronic lymphocytic leukemia (CLL) is characterized by a strong familial risk, the genetic basis of inherited susceptibility to CLL is largely unknown. The increased risk of Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) in relatives of CLL patients suggests a common etiology to B-cell lymphoproliferative disorders (LPDs) through HLA variation.1 Moreover, as B-cell proliferation is part of an adaptive immune response, which can be initiated by major histocompatibility complex (MHC)-restricted T-cell activation, a possible influence of HLA on CLL pathogenesis is plausible.

It has recently been demonstrated that single nucleotide polymorphism (SNP) variation within the 6p21 region can accurately predict alleles at HLA-A, HLA-B, HLA-C, HLA-DRB1, HLA-DQA1 and HLA-DQB1 loci.2 Furthermore, HLA alleles can be accurately predicted from the SNPs used in a genome-wide association study (GWAS). To investigate the role of genetic variation in the MHC region in the etiology of CLL, we have applied this methodology to SNP data from a GWAS of CLL.

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Acknowledgements

Leukemia Lymphoma Research provided principal funding for the study. Additional funding was provided by Cancer Research UK and the Arbib fund. We acknowledge National Health Service funding for the Royal Marsden Biomedical Research Center. Finally we are grateful to all individuals for their participation.

Web Resources

Human Chromosome 6 Project Overview: http://www.sanger.ac.uk/HGP/Chr6

British 1958 birth cohort: http://www.b58cgene.sgul.ac.uk

NCBI dbSNP: http://www.ncbi.nlm.nih.gov/SNP/

Online Mendelian Inheritance in Man (OMIM): http://www.ncbi.nlm.nih.gov/Omim/

Illumina: http://www.illumina.com/

Golden Helix: http://www.goldenhelix.com/

HLA*IMP: http://oxfordhla.well.ox.ac.uk/hla/

NSCCG: http://www.icr.ac.uk/research/team_leaders/Houlston_Richard/Houlston_Richard_RES/NSCCG/index.shtml

CLL4: http://www.icr.ac.uk/research/research_divisions/Molecular_Pathology/CLL4_trial/index.shtml

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Authors and Affiliations

  1. Division of Genetics and Epidemiology, Molecular and Population Genetics, Institute of Cancer Research, Surrey, UK

    M C Di Bernardo, P Broderick, S Harris & R S Houlston

  2. Deptartment of Cancer Studies and Molecular Medicine, Leicester University, Leicester, UK

    M J S Dyer

  3. Division of Pathology, Section of Haemato-Oncology, Institute of Cancer Research, Surrey, UK

    E Matutes, C Dearden & D Catovsky

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  1. M C Di Bernardo
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  2. P Broderick
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  3. S Harris
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  4. M J S Dyer
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  6. C Dearden
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  7. D Catovsky
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  8. R S Houlston
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Correspondence to R S Houlston.

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Di Bernardo, M., Broderick, P., Harris, S. et al. Risk of developing chronic lymphocytic leukemia is influenced by HLA-A class I variation. Leukemia 27, 255–258 (2013). https://doi.org/10.1038/leu.2012.173

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