A 60-year-old man presents with painless cervical lymphadenopathy. Biopsy shows a nodular proliferation of small cleaved B cells with a t(14;18) translocation. The translocation causes lymphomagenesis primarily by which mechanism?

• A Loss of TP53 function, removing DNA damage checkpoints
• B Activation of MYC, driving uncontrolled cellular proliferation
• C Overexpression of BCL2, which inhibits mitochondrial outer membrane permeabilization ✓
• D Constitutive activation of the BCR-ABL tyrosine kinase

Explanation

t(14;18) places the BCL2 gene under control of the immunoglobulin heavy chain promoter, causing anti-apoptotic BCL2 overexpression. BCL2 binds and sequesters BH3-only activators and prevents BAX and BAK oligomerization, blocking cytochrome c release and intrinsic apoptosis, allowing survival of B cells that should die. MYC activation defines Burkitt lymphoma (t(8;14)), and BCR-ABL defines CML, making those distractors tempting but wrong here.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.