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The biology and clinical significance of acquired genomic copy number aberrations and recurrent gene mutations in chronic lymphocytic leukemia

Oncogene volume 32, pages 2805–2817 (2013)Cite this article

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Abstract

Chronic lymphocytic leukemia (CLL) is the most common leukemia in the Western world and remains incurable with conventional chemotherapy treatment approaches. CLL as a disease entity is defined by a relatively parsimonious set of diagnostic criteria and therefore likely constitutes an umbrella term for multiple related illnesses. Of the enduring fundamental biological processes that affect the biology and clinical behavior of CLL, few are as central to the pathogenesis of CLL as recurrent acquired genomic copy number aberrations (aCNA) and recurrent gene mutations. Here, a state-of-the-art overview of the pathological anatomy of the CLL genome is presented, including detailed descriptions of the anatomy of aCNA and gene mutations. Data from SNP array profiling and large-scale sequencing of large CLL cohorts, as well as stimulated karyotyping, are discussed. This review is organized by discussions of the anatomy, underlying pathomechanisms and clinical significance of individual genomic lesions and recurrent gene mutations. Finally, gaps in knowledge regarding the biological and clinical effects of recurrent genomic aberrations or gene mutations on CLL are outlined to provide critical stimuli for future research.

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Acknowledgements

This research is supported by the National Institutes of Health through R01 CA136537-01 (SM), the Translational Research Program of the Leukemia and Lymphoma Society of America (SM), the Scholars in Clinical Research Program of the Leukemia and Lymphoma Society of America (SM) and a CLL collaborative grant from the Lymphoma Research Foundation. This research is supported (in part) by the National Institutes of Health through the University of Michigan’s Cancer Center Support Grant (5 P30 CA46592) and Oncology Research Training Grant (T32 CA 009357-30). I am grateful for services provided by the microarray core of the University of Michigan Comprehensive Cancer Center.

Author contributions: Sami N Malek wrote the paper.

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  1. Department of Internal Medicine, Division of Hematology and Oncology, University of Michigan, Ann Arbor, MI, USA

    S N Malek

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Dr Malek’s work has been funded by the NIH, the Leukemia and Lymphoma Society of America and the Lymphoma Research Foundation. He has received honoraria from Roche and Teva.

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Malek, S. The biology and clinical significance of acquired genomic copy number aberrations and recurrent gene mutations in chronic lymphocytic leukemia. Oncogene 32, 2805–2817 (2013). https://doi.org/10.1038/onc.2012.411

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