Journal
SEMINARS IN CANCER BIOLOGY
Volume 24, Issue -, Pages 71-81Publisher
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.semcancer.2013.08.011
Keywords
Chronic lymphocytic leukemia; CLL; Microenvironment; Nurselike cells; Stromal cells; CXCR4; CXCL12; B cell receptor; BCR; SYK; BTK; PI3K delta; Chemokines; Chemokine receptors; T cells; NK cells
Categories
Funding
- CLL Global Research Foundation
- Leukemia & Lymphoma Society Scholar Award in Clinical Research
- Cancer Prevention and Research Institute of Texas (CPRIT)
- NIH
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Over the last decade, the active role of the microenvironment in the pathogenesis of B cell lymphomas has been recognized, delivering signals that favor clonal expansion and drug resistance. We are only beginning to understand the complex cross talk between neoplastic B cells and the tissue microenvironment, for example in secondary lymphoid organs, but some key cellular and molecular players have emerged. Mesenchymal stromal cells, nurselike cells (NLC) and lymphoma-associated macrophages (LAM), in concert with T cells, natural killer cells and extracellular matrix components participate in the dialog with the neoplastic B cells. B cell receptor signaling, activation via TNF family members (i.e. BAFF, APRIL), and tissue homing chemokine receptors and adhesion molecules are important in the interaction between malignant B cells and their microenvironment Disrupting this cross talk is an attractive novel strategy for treating patients with B cell malignancies. Here, we summarize the cellular and molecular interactions between B cell lymphoma/leukemia cells and their microenvironment, and the therapeutic targets that are emerging, focusing on small molecule inhibitors that are targeting B cell receptor-associated kinases SYK, BTK, and PI3Ks, as well as on immunomodulatory agents and T cell mediated therapies. Clinically relevant aspects of new targeted therapeutics will be discussed, along with an outlook into future therapeutic strategies. (C) 2013 Elsevier Ltd. All rights reserved.
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