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B-cell lymphoma protein w (BCL-W)

Target: BCL-W
Molecular classification: Anti-apoptotic protein, BCL-2 family protein

Overview

B-cell lymphoma protein w (BCL-W, encoded by BCL2L2) is a member of the anti-apoptotic BCL-2 protein family. BCL-W antagonizes apoptosis by binding and sequestering pro-apoptotic members of the BCL-2 family, preventing mitochondrial membrane permeabilization and cell death. High expression of BCL-W is observed in several types of human lymphomas, including diffuse large B-cell lymphoma, follicular lymphoma, Burkitt lymphoma, and mantle cell lymphoma. Overexpression of BCL-W is associated with enhanced lymphoma cell survival, resistance to cytotoxic agents, and poor prognosis, particularly in DLBCL cases with low BCL-2 expression. Knockdown or inhibition of BCL-W induces apoptosis in lymphoma cells and sensitizes them to chemotherapy, establishing BCL-W as a potential therapeutic target in B-cell lymphomas.

Other names: Bcl-wBCL2-like 2BCL2L2

Mechanism of action

Inhibition of BCL-W disrupts its anti-apoptotic interaction with pro-apoptotic proteins, inducing apoptosis in lymphoma cells

Biological functions

Regulation of apoptosisPromotion of cell survival

Disease associations

CancerLymphoma

Safety considerations

On-target toxicity to normal cells depending on BCL-W for survival (notably, germ cells; knockout models show impaired spermatogenesis; potential hematopoietic or other tissue toxicity if selectively inhibited)

Interacting drugs

Experimental BCL-2 family inhibitors (e.g., navitoclax may inhibit BCL-W among other anti-apoptotic BCL-2 family proteins, but currently no clinically approved BCL-W selective inhibitor)

Biomarkers

BCL-W expression (high BCL-W mRNA/protein can serve as a biomarker for prognosis in several B-cell lymphomas)

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