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Hematologic Cancers: From Molecular Pathobiology to Targeted Therapeutics pp 53–82Cite as

Genetic and Environmental Determinants in Multiple Myeloma: Implications for Therapy

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Part of the book series: Cancer Growth and Progression ((CAGP,volume 14))

Abstract

Multiple myeloma is an incurable hematopoietic malignancy linked to more than 10,000 deaths annually. This dyscrasia is associated with significant co-morbidities as a result of the clonal expansion of bone marrow resident, immunoglobulin secreting, plasma cells. As will most cancers, myeloma tumorigenesis is a defined by both genetic transforming events and the growth and survival factors provided by the bone marrow microenvironment. The earliest genetic aspects of myeloma tumorigenesis have been shown to result from non-random translocations of genes that normally function as determinants of cell proliferation or cell survival to regions juxtaposed to active immunoglobulin heavy chain (IgH) enhancer elements, Secondary somatic mutations are then acquired that affect oncogenic signaling via Ras, Raf, NF-κB, FGFR3, or myc. Further, the loss of tumor suppressor function with deletion of the short of arm of chromosome 17 as later events. These events have been characterized over the last several decades and provide a model for the progression from the premalignant MGUS (monoclonal gammopathy of undetermined significance), to smoldering myeloma, to active myeloma, to extramedually plasma cell leukemia, and cells lines. Even in the setting of a genetic disease, it has long been appreciated that the bone marrow microenvironment also promotes multiple myeloma cell pathogenesis and has become an important target for therapeutic intervention. With increased understanding of the both the genetics of myeloma and the bone marrow niche numerous novel therapies are underdevelopment that will be discussed within this book chapter with the anticipation of improved clinical outcomes.

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Authors and Affiliations

  1. Experimental Therapeutics Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA

    Kenneth H. Shain M.D., Ph.D.

  2. Experimental Therapeutics Program, Departments of Experimental Therapeutics and Oncologic Sciences, H. Lee Moffitt Cancer Center and Research Institute, University of South Florida, 12902 Magnolia Drive, Tampa, 33612, FL, USA

    William S. Dalton Ph.D., M.D.

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  1. Research Institute, Department of Hematopathology and, H. Lee Moffitt Cancer Center &, Magnolia Drive - MCC-LAB 12902, Tampa, 33612, Florida, USA

    Jianguo Tao

  2. Research Institute, Department of Malignant Hematology, H. Lee Moffitt Cancer Center &, Magnolia Drive 12902, Tampa, 33612, Florida, USA

    Eduardo Sotomayor

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Shain, K.H., Dalton, W.S. (2012). Genetic and Environmental Determinants in Multiple Myeloma: Implications for Therapy. In: Tao, J., Sotomayor, E. (eds) Hematologic Cancers: From Molecular Pathobiology to Targeted Therapeutics. Cancer Growth and Progression, vol 14. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-5028-9_4

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