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Apoptosis Pathways in Chronic Lymphocytic Leukemia: Role of the Microenvironment and Therapeutic Strategies

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Multi-Targeted Approach to Treatment of Cancer

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Abstract

Chronic lymphocytic leukemia (CLL) is a B‐cell malignancy marked by defective apoptosis and apoptotic resistance. CLL lymphocytes accumulate in bone marrow, lymph nodes, and peripheral blood and receive survival signals through a diverse microenvironment in these body compartments. CLL microenvironment and cell interactions have been studied extensively. The microenvironment aggravates the antiapoptotic components in CLL cells and depletes the proapoptotic signaling that is essential to defending against apoptosis resistance. Ample research has been conducted to understand the involvement of apoptosis pathway proteins and the role of the microenvironment in the biology of leukemic cells. Major protein groups of the apoptosis pathway are the B‐cell lymphoma 2 (Bcl-2) family, inhibitor of apoptosis protein (IAP) family, nuclear factor kappa‐light‐chain‐enhancer of activated B cells (NF-kB) signaling axis, tumor necrosis factor receptor superfamily (TNFRSF), B-cell receptor (BCR), death effector domain-containing proteins (DED) family, caspase activation and recruitment domain-containing proteins (CARD) family, and the caspase family. Here, we review the role of apoptosis pathway protein groups in the CLL microenvironment and strategies to counter survival signals of these groups as approaches in CLL therapy.

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Acknowledgments

The authors gratefully acknowledge Markeda Wade from Scientific Publication for critically reviewing and editing the manuscript. This work was supported in part by grant P01 CA81534 from the National Cancer Institute, a CLL Global Research Foundation Alliance grant award, and generous philanthropic contributions to The University of Texas MD Anderson Cancer Center Moon Shot Program.

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Authors and Affiliations

  1. Departments of Experimental Therapeutics, The University of Texas M.D. Anderson Cancer Center, 301429, Houston, TX, USA

    Viralkumar Patel, Kumudha Balakrishnan & Varsha Gandhi

  2. Departments of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Varsha Gandhi

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  1. Viralkumar Patel
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  2. Kumudha Balakrishnan
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  3. Varsha Gandhi
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Correspondence to Varsha Gandhi .

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Editors and Affiliations

  1. Department of Experimental Therapeutics, University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA

    Varsha Gandhi

  2. Department of Experimental Therapeutics, University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA

    Kapil Mehta

  3. Delhi State Cancer Institute (East), Delhi, India

    Rajesh Grover

  4. Department of Experimental Therapeutics, University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA

    Sen Pathak

  5. Department of Bioimmunotherapy, Section of Cytokine Research, University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA

    Bharat B. Aggarwal

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Patel, V., Balakrishnan, K., Gandhi, V. (2015). Apoptosis Pathways in Chronic Lymphocytic Leukemia: Role of the Microenvironment and Therapeutic Strategies. In: Gandhi, V., Mehta, K., Grover, R., Pathak, S., Aggarwal, B. (eds) Multi-Targeted Approach to Treatment of Cancer. Adis, Cham. https://doi.org/10.1007/978-3-319-12253-3_4

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