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The tumor microenvironment shapes hallmarks of mature B-cell malignancies

Oncogene volume 34, pages 4673–4682 (2015)Cite this article

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Abstract

B-cell tumorigenesis results from a host of known and unknown genetic anomalies, including non-random translocations of genes that normally function as determinants of cell proliferation or cell survival to regions juxtaposed to active immunoglobulin heavy chain enhancer elements, chromosomal aneuploidy, somatic mutations that further affect oncogenic signaling and loss of heterozygosity of tumor-suppressor genes. However, it is critical to recognize that even in the setting of a genetic disease, the B-cell/plasma cell tumor microenvironment (TME) contributes significantly to malignant transformation and pathogenesis. Over a decade ago, we proposed the concept of cell adhesion-mediated drug resistance to delineate a form of TME-mediated drug resistance that protects hematopoietic tumor cells from the initial effect of diverse therapies. In the interim, it has been increasingly appreciated that TME also contributes to tumor initiation and progression through sustained growth/proliferation, self-renewal capacity, immune evasion, migration and invasion as well as resistance to cell death in a host of B-cell malignancies, including mantle cell lymphoma, diffuse large B-cell lymphoma, Waldenstroms macroglobulinemia, chronic lymphocytic leukemia and multiple myeloma. Within this review, we propose that TME and the tumor co-evolve as a consequence of bidirectional signaling networks. As such, TME represents an important target and should be considered integral to tumor progression and drug response.

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Acknowledgements

This work was supported by the Department of Health Bankhead-Coley Team Science Program grant (2BT03), the US Army Medical Research and Materiel Command under Award W81XWH-08-2-0101 for a National Functional Genomics Center, the National Cancer Institute under Award (P30-CA076292), National Cancer Institutes (R01CA137123), Lymphoma Research Foundation, Maher Fund and the Moffitt Cancer Center Foundation.

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All the authors preformed the literature review, wrote and approved the manuscript.

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Authors and Affiliations

  1. Department of Malignant Hematology and Chemical Biology and Molecular Medicine Program, Tampa, FL, USA

    K H Shain & W S Dalton

  2. DeBartolo Family Personalized Medicine Institute, Tampa, FL, USA

    W S Dalton

  3. Department of Hematopathology and Laboratory Medicine, Moffitt Cancer Center and Research Institute at the University of South Florida, Tampa, FL, USA

    J Tao

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  1. K H Shain
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  2. W S Dalton
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Correspondence to K H Shain or J Tao.

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Shain, K., Dalton, W. & Tao, J. The tumor microenvironment shapes hallmarks of mature B-cell malignancies. Oncogene 34, 4673–4682 (2015). https://doi.org/10.1038/onc.2014.403

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