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Apoptosis of Multiple Myeloma

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Abstract

Multiple myeloma (MM) is a malignancy of terminally differentiated plasma cells. MM cells localize to the bone marrow, where cell adhesion-mediated autocrine or paracrine activation of various cytokines, such as interleukin 6, insulin-like growth factor 1, and interferon α, results in their accumulation mainly because of loss of critical apoptotic controls. Resistance to apoptosis, a genetically regulated cell death process, may play a critical role in both pathogenesis and resistance to treatment of MM.Abnormalities in regulation and execution of apoptosis can contribute to tumor initiation, progression, as well as to tumor resistance to various therapeutic agents. Apoptosis is executed via 2 main pathways that lead to activation of caspases: the death receptor (extrinsic) pathway and the mitochondrial (intrinsic) pathway. Ionizing radiation and chemotherapeutic agents act primarily through the intrinsic pathway, in which mitochondria play the central role. Various therapeutic modalities that are effective in MM modulate levels of the proapoptotic and antiapoptotic Bcl-2 family of proteins and of inhibitors of apoptosis, expression of which is primarily regulated by p53, nuclear factor κB, and STAT (signal transducers and activators of transcription) factors.This review focuses on the key concepts and some of the most recent studies of signaling pathways regulated in MM and summarizes what is known about the clinical role of these pathways.

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Authors and Affiliations

  1. Departments of Cancer Biology and Radiation Oncology Lerner Research Institute, Cleveland Clinic Foundation, NB40, 44195, Cleveland, OH, USA

    Marcela Oancea & Alexandru Almasan

  2. Myeloma Program, NB40, 44195, Cleveland, OH, USA

    Aruna Mani & Mohamad A. Hussein

  3. Departments of Radiation Oncology, Taussig Cancer Center, NB40, 44195, Cleveland, OH, USA

    Alexandru Almasan

  4. Department of Chemistry, Cleveland State University, NB40, 44195, Cleveland, OH, USA

    Marcela Oancea

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  1. Marcela Oancea
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  2. Aruna Mani
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  3. Mohamad A. Hussein
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  4. Alexandru Almasan
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Correspondence to Alexandru Almasan.

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Oancea, M., Mani, A., Hussein, M.A. et al. Apoptosis of Multiple Myeloma. Int J Hematol 80, 224–231 (2004). https://doi.org/10.1532/IJH97.04107

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