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Inhibiting B-Cell Receptor Signaling Pathways in Chronic Lymphocytic Leukemia

  • Chronic Lymphocytic Leukemia (S O’Brien, Section Editor)
  • Published:
Current Hematologic Malignancy Reports Aims and scope Submit manuscript

Abstract

B-cell receptor (BCR) signaling is a central pathologic mechanism in B-cell malignancies, including chronic lymphocytic leukemia (CLL), in which it promotes leukemia cell survival and proliferation, and modulates CLL cell migration and tissue homing. BCR signaling now can be targeted with new, small molecule inhibitors of the spleen tyrosine kinase (Syk), Bruton’s tyrosine kinase (Btk), or phosphoinositide 3′-kinase (PI3K) isoform p110δ (PI3Kδ), which have recently entered the clinical stage and show promising results in patients with CLL. During the first weeks of therapy, these agents characteristically induce rapid resolution of lymphadenopathy and organomegaly, accompanied by a transient surge in lymphocyte counts due to “mobilization” of tissue-resident CLL cells into the blood. Then, often after months of continuous therapy, a major proportion of patients achieve remissions. This article reviews key biologic aspects of BCR-associated kinases in CLL and other B cell neoplasias, and develops perspectives for future development of this exciting new class of kinase inhibitors.

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Acknowledgments

This manuscript was supported by a CLL Global Research Foundation grant and a Cancer Prevention and Research Institute of Texas (CPRIT) grant (to J.A.B.).

Disclosure

Conflicts of Interest: J. Burger: Research funding grants (in addition to those mentioned above) from Calistoga, Genzyme, Gilead, and Pharmacyclics; consulting fees from Genzyme, Noxxon, and Pharmacyclics.

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  1. Department of Leukemia, Unit 428, The University of Texas M.D. Anderson Cancer Center, P.O. Box 301402, Houston, TX, 77230-1402, USA

    Jan A. Burger

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Burger, J.A. Inhibiting B-Cell Receptor Signaling Pathways in Chronic Lymphocytic Leukemia. Curr Hematol Malig Rep 7, 26–33 (2012). https://doi.org/10.1007/s11899-011-0104-z

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