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  • Review Article
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Chronic lymphocytic leukaemia: from genetics to treatment

Nature Reviews Clinical Oncology volume 16, pages 684–701 (2019)Cite this article

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Abstract

Chronic lymphocytic leukaemia (CLL), the most frequent type of leukaemia in adults, is a lymphoproliferative disorder that is characterized by the expansion of monoclonal, mature CD5+CD23+ B cells in the peripheral blood, secondary lymphoid tissues and bone marrow. CLL is an incurable disease with a heterogeneous clinical course, for which the treatment decision still relies on conventional parameters (such as clinical stage and lymphocyte doubling time). During the past 5 years, relevant advances have been made in understanding CLL biology. Indeed, substantial progress has been made in the identification of the putative cell of origin of CLL, and comprehensive studies have dissected the genomic, epigenomic and transcriptomic landscape of CLL. Advances in clinical management include improvements in our understanding of the prognostic value of different genetic lesions, particularly those associated with chemoresistance and progression to highly aggressive forms of CLL, and the advent of new therapies targeting crucial biological pathways. In this Review, we discuss new insights into the genetic lesions involved in the pathogenesis of CLL and how these genetic insights influence clinical management and the development of new therapeutic strategies for this disease.

Key points

  • Next-generation sequencing of the coding genome has identified the most common somatic genetic alterations associated with the pathogenesis of chronic lymphocytic leukaemia (CLL).

  • Specific genetic alterations provide biomarkers for prognostication of the clinical course and prediction of response to chemotherapy and targeted therapy.

  • Recurrent genetic alterations identify cellular pathways that present potential therapeutic targets.

  • This new knowledge is informing novel treatment algorithms for the clinical management of patients with CLL.

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Fig. 1: The cellular origin of chronic lymphocytic leukaemia.
Fig. 2: CLL genetic landscape and currently tested targeted drugs.
Fig. 3: Genetics of chronic lymphocytic leukaemia progression.
Fig. 4: Therapeutic algorithm for patients with CLL.

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Acknowledgements

The work of the authors is supported by grants to F.B. from the Ministry of Economy and Competitiveness, Instituto de Salud Carlos III (17/00943) and to R.D.-F. from the US Department of Health & Human Services, NIH, National Cancer Institute (NCI) (1R35CA210105).

Reviewer information

Nature Reviews Clinical Oncology thanks S. Stilgenbauer, J. Burger and M. Hallek, for their contribution to the peer review of this work.

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  1. Department of Haematology, University Hospital Vall d’Hebron, Autonomous University, Barcelona, Spain

    Francesc Bosch

  2. Laboratory of Experimental Haematology, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain

    Francesc Bosch

  3. Institute for Cancer Genetics, Columbia University, New York, NY, USA

    Francesc Bosch & Riccardo Dalla-Favera

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Bosch, F., Dalla-Favera, R. Chronic lymphocytic leukaemia: from genetics to treatment. Nat Rev Clin Oncol 16, 684–701 (2019). https://doi.org/10.1038/s41571-019-0239-8

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