Chronic lymphocytic leukaemia (CLL) is a malignancy of CD5+ B cells that is characterized by the accumulation of small, mature-appearing lymphocytes in the blood, marrow and lymphoid tissues. Signalling via surface immunoglobulin, which constitutes the major part of the B cell receptor, and several genetic alterations play a part in CLL pathogenesis, in addition to interactions between CLL cells and other cell types, such as stromal cells, T cells and nurse-like cells in the lymph nodes. The clinical progression of CLL is heterogeneous and ranges from patients who require treatment soon after diagnosis to others who do not require therapy for many years, if at all. Several factors, including the immunoglobulin heavy-chain variable region gene (IGHV) mutational status, genomic changes, patient age and the presence of comorbidities, should be considered when defining the optimal management strategies, which include chemotherapy, chemoimmunotherapy and/or drugs targeting B cell receptor signalling or inhibitors of apoptosis, such as BCL-2. Research on the biology of CLL has profoundly enhanced our ability to identify patients who are at higher risk for disease progression and our capacity to treat patients with drugs that selectively target distinctive phenotypic or physiological features of CLL. How these and other advances have shaped our current understanding and treatment of patients with CLL is the subject of this Primer.
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The authors thank H.-Y. Wang and E. Broome, Department of Pathology, University of California San Diego, for their contributions to Figures 5–7. The authors also thank A. Greaves, University of California San Diego, for help in figure development. This Primer is supported by the US NIH PO1-CA81534 for the CLL Research Consortium; members include K.R., W.G.W., T.J.K., C.M.C., C.J.W. and J.G. The authors also acknowledge support to F.K.S. and G.P. from Bloodwise, Kay Kendall Leukaemia Fund, Cancer Research UK, the Southampton Experimental Cancer Medicine Centre, and the Southampton Cancer Research UK Centre (F.K.S. and G.P.). The authors also acknowledge support from the Leukemia & Lymphoma Society (LLS) Specialized Center of Research Program (SCOR) grant (T.J.K.), 1R01HL116452, 1R01CA182461, CLL Global Reseach Foundation (W.G.W.), the Blood Cancer Research Fund (T.J.K.), and U10CA180861.
J.G. has received honoraria for advisory boards from Roche, Genentech, AbbVie, Janssen, Pharmacyclics, Acerta, Gilead, TG Therapeutics and Unum. S.O. has acted as a consultant for Amgen and Celgene, is a scientific advisory board member for CLL Global Research Foundation and has received research support from Acerta, TG Therapeutics, Regeneron, Gilead, Pharmacyclics and ProNAi. K.R. is a member of the medical advisory board for Celgene, Roche/Genetech, Pharmacyclics and Gilead. T.J.K. has received honoraria for Ad boards, meetings, presentations and/or consulting from Gilead, Pharmacyclics, Celgene, Roche and AbbVie, and has received research funding from AbbVie and Celgene. C.J.W. is a co-founder and a member of the scientific advisory board of Neon Therapeutics. W.G.W., G.P., C.M.C. and F.K.S. declare no competing interests.
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Kipps, T., Stevenson, F., Wu, C. et al. Chronic lymphocytic leukaemia. Nat Rev Dis Primers 3, 16096 (2017). https://doi.org/10.1038/nrdp.2016.96
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