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Male preponderance in chronic lymphocytic leukemia utilizing IGHV 1–69

Leukemia volume 21, pages 2537–2538 (2007)Cite this article

Gender plays an important role in the incidence, progression and prognosis of individuals with several forms of hematological malignancy. In the context of B-cell lymphoproliferative disorders, there is a marked preponderance of men (4:1 male to female ratio) in diseases such as hairy cell leukemia.1 For chronic lymphocytic leukemia (CLL), data derived from both national registries and from prospective clinical trials have shown an increased incidence of men (reviewed in Molica2). One registry study reported a fivefold excess of men in patients presenting at about 40 years of age.3 Men tend to present with more clinically advanced disease and have a worse prognosis. Randomized clinical trials have shown that even allowing for clinical stage, men have a worse prognosis than women. The biological basis for these differences remains unclear; possible explanations include molecular, genetic and hormonal differences.

Studies on the expression of the immunoglobulin (IG) V region gene segments in CLL have revealed a number of biologically and clinically interesting points. First, there are two subsets of CLL that can be defined by the presence or absence of somatic mutations. Presence of somatic mutations is associated with a better prognosis. In one previous study, there was a 2:1 male excess in CLL patients with unmutated disease, whereas the mutated CLL showed male to female equivalence.4 Second, several studies have shown highly restricted IG rearrangements in CLL, both in terms of IGHV gene segment usage and in terms of antigen-binding sequences, suggesting a strong role for antigen selection during the development of the disease.5 A number of the ‘stereotypical’ IG receptors involve the IGHV1–69 gene segments. IGHV1–69 gene segment usage is found in about 10–15% of all CLL patients. In most instances, these segments remain unmutated. Sequence analysis of both heavy- and light-chain gene sequences has shown strong conservation of the antigen-binding site.

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Author notes

  1. R Walewska and A Majid: These two authors contributed equally to this work.

Authors and Affiliations

  1. The MRC Toxicology Unit/University of Leicester, Hodgkin Building, Leicester, UK

    R Walewska, A Majid, P Dusanjh & M J S Dyer

  2. Department of Haematology, Royal Bournemouth Hospital, Castle Lane East, Bournemouth, UK

    Z Davis & D G Oscier

  3. Department of Haematology, University Hospitals, Leicester, UK

    D B J Kennedy

Authors
  1. R Walewska
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  2. A Majid
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  3. Z Davis
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  4. P Dusanjh
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  5. D B J Kennedy
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  6. D G Oscier
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  7. M J S Dyer
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Corresponding author

Correspondence to M J S Dyer.

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Supported by grants from the Medical Research Council, from the Hope Foundation and the Leukaemia Research Fund.

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Walewska, R., Majid, A., Davis, Z. et al. Male preponderance in chronic lymphocytic leukemia utilizing IGHV 1–69. Leukemia 21, 2537–2538 (2007). https://doi.org/10.1038/sj.leu.2404836

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