A 60-year-old man presents with painless generalized lymphadenopathy. Lymph node biopsy shows a nodular proliferation of centrocytes and centroblasts. Molecular analysis demonstrates a balanced translocation placing the BCL2 gene under control of the immunoglobulin heavy chain promoter. The resulting overexpression of BCL2 promotes lymphomagenesis primarily by:

• A Driving uncontrolled cellular proliferation through cyclin D1 upregulation
• B Impairing nucleotide excision repair of DNA damage
• C Activating tyrosine kinase signaling constitutively
• D Inhibiting apoptosis by blocking cytochrome c release from mitochondria ✓

Explanation

The t(14;18) translocation of follicular lymphoma juxtaposes BCL2 with the IgH enhancer, causing overexpression of the anti-apoptotic BCL2 protein, which prevents mitochondrial outer membrane permeabilization and cytochrome c release, thereby blocking caspase activation. This is the prototypical example of a lymphoma driven by failure of programmed cell death rather than increased proliferation. Cyclin B1 upregulation results from t(11;14) in mantle cell lymphoma, and constitutive tyrosine kinase activation exemplifies BCR-ABL in chronic myeloid leukemia.

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.