title: The B-cell receptor orchestrates environment-mediated lymphoma survival and drug resistance in B-cell malignancies.
abstract: Specific niches within the lymphoma tumor microenvironment (TME) provide sanctuary for subpopulations of tumor cells through stromal cell-tumor cell interactions. These interactions notably dictate growth, response to therapy and resistance of residual malignant B cells to therapeutic agents. This minimal residual disease (MRD) remains a major challenge in the treatment of B-cell malignancies and contributes to subsequent disease relapse. B-cell receptor (BCR) signaling has emerged as essential mediator of B-cell homing, survival and environment-mediated drug resistance (EMDR). Central to EMDR are chemokine- and integrin-mediated interactions between lymphoma and the TME. Further, stromal cell-B cell adhesion confers a sustained BCR signaling leading to chemokine and integrin activation. Recently, the inhibitors of BCR signaling have garnered a substantial clinical interest because of their effectiveness in B-cell disorders. The efficacy of these agents is, at least in part, attributed to attenuation of BCR-dependent lymphoma-TME interactions. In this review, we discuss the pivotal role of BCR signaling in the integration of intrinsic and extrinsic determinants of TME-mediated lymphoma survival and drug resistance.
authors.affiliation: Departments of Malignant Hematology and Chemical Biology and Molecular Medicine Program, H Lee Moffitt Cancer Center and Research Institute at the University of South Florida, Tampa, FL, USA.
authors.forename: K H
authors.initials: KH
authors.lastname: Shain
authors.affiliation: Departments of Hematopathology and Laboratory Medicine, and Chemical Biology and Molecular Medicine Program, H Lee Moffitt Cancer Center and Research Institute at the University of South Florida, Tampa, FL, USA.
authors.forename: J
authors.initials: J
authors.lastname: Tao
mesh_terms: D001402:B-Lymphocytes / Q000166:cytology; D002448:Cell Adhesion; D002470:Cell Survival; D019008:Drug Resistance, Neoplasm; D006801:Humans; D008223:Lymphoma / Q000188:drug therapy* / Q000401:mortality*; D016393:Lymphoma, B-Cell / Q000503:physiopathology*; D018365:Neoplasm, Residual; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism*; D015398:Signal Transduction; D017154:Stromal Cells / Q000378:metabolism
chemical_list: D011947:Receptors, Antigen, B-Cell
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