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Germline mutations in SPI1 and MADD do not contribute to familial chronic lymphocytic leukaemia

Leukemia volume 21, pages 1315–1318 (2007)Cite this article

Chronic lymphocytic leukaemia (CLL) is the most common form of leukaemia accounting for around 30% of all cases. Inherited predisposition to CLL is now well established, with epidemiological studies showing 3–7-fold elevations of risk in first-degree relatives of CLL cases.1 Although no gene, which when mutated in the germline, has been shown to unambiguously confer susceptibility to the disease, we have, recently localized a disease locus on chromosome 11p11.2 Two genes SPI1 (encoding PU.1) and MADD (Mendelian inheritance in man: 165170 and 603584) localize to 11p11 and represent pre-eminent candidate susceptibility genes a priori.

PU.1 has recently attracted considerable attention as a major player in haematoproliferative differentiation.3 PU.1, a member of the ETS family of transcription factors, is upregulated during normal haematopoiesis, but specifically in mature myeloid and B cells influencing the expression of a number of key proteins, including colony-stimulating factor and immunoglobulin subunits (overviewed in Okuno et al.4) In mice disruption of both alleles of SPI1 results in profound defects in the development of both lymphoid and myeloid cell lineages. Moreover, loss of SPI1 expression has been shown to cause acute myeloid leukaemia (AML) in mice, and heterozygous mutations have been documented in AML patients.5

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Acknowledgements

We are grateful to all patients and control individuals for their participation in this study. Work was undertaken with support from Leukemia Research and the Arbib Foundation.

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Authors and Affiliations

  1. Section of Cancer Genetics, Institute of Cancer Research, Sutton, Surrey, UK

    G S Sellick, M Qureshi, S Fielding & R S Houlston

  2. Section of Haemato-Oncology, Institute of Cancer Research, Sutton, Surrey, UK

    D Catovsky

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  1. G S Sellick
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  2. M Qureshi
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  3. S Fielding
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  4. D Catovsky
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  5. R S Houlston
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Correspondence to R S Houlston.

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Sellick, G., Qureshi, M., Fielding, S. et al. Germline mutations in SPI1 and MADD do not contribute to familial chronic lymphocytic leukaemia. Leukemia 21, 1315–1318 (2007). https://doi.org/10.1038/sj.leu.2404646

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