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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