A 35-year-old woman with B-cell lymphoma has tumor cells demonstrating t(14;18) translocation. This translocation juxtaposes the BCL2 gene next to immunoglobulin heavy chain locus, resulting in overexpression of BCL2. What is the primary anti-apoptotic mechanism of BCL2 protein?

• A Direct caspase-9 cleavage and inactivation in the cytoplasm
• B Upregulation of XIAP to block executioner caspases 3 and 7
• C Sequestration of cytochrome c released into the cytoplasm
• D Inhibition of BAX/BAK pore formation in the outer mitochondrial membrane ✓

Explanation

BCL2 is an anti-apoptotic protein residing in the outer mitochondrial membrane that functions by binding and sequestering pro-apoptotic BH3-only proteins and inhibiting BAX/BAK oligomerisation. BAX and BAK form pores (MOM permeabilisation) that release cytochrome c, which triggers the apoptosome and caspase cascade; BCL2 prevents this pore formation. t(14;18) is the hallmark translocation of follicular lymphoma, where overexpression of BCL2 confers resistance to apoptosis.

Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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