A 35-year-old woman has follicular lymphoma. Biopsy shows BCL2 overexpression due to t(14;18)(q32;q21). The mechanism by which this translocation drives lymphomagenesis is:

• A BCL2 gain-of-function promotes cell proliferation by activating CDK4/6
• B BCL2 promotes autophagy allowing tumor cells to survive nutrient deprivation
• C BCL2 activates PI3K-AKT signaling bypassing growth factor receptor requirements
• D BCL2 overexpression blocks apoptosis by preventing cytochrome c release from mitochondria ✓

Explanation

BCL2 is an anti-apoptotic protein located on the outer mitochondrial membrane; it inhibits BAX/BAK-mediated pore formation, thereby preventing cytochrome c release, which would otherwise activate caspase-9 via the apoptosome (intrinsic apoptosis pathway). The t(14;18) places BCL2 under IGH enhancer control causing constitutive overexpression. This alone does not accelerate proliferation (explaining the low-grade, indolent behavior of follicular lymphoma), but prevents B-cells from undergoing programmed death. Venetoclax (BCL2 inhibitor) exploits this dependency.

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

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Written and medically reviewed by the StethoPrep medical team.