A 62-year-old man presents with painless cervical lymphadenopathy. Biopsy of the node shows a nodular proliferation of small cleaved lymphocytes with interspersed centroblasts, and immunohistochemistry demonstrates strong BCL2 expression within germinal centers. The oncogenic significance of this protein overexpression lies in its ability to:

• A Activate caspase-8 downstream of the death receptor
• B Inhibit apoptosis by preventing cytochrome c release from mitochondria ✓
• C Drive uncontrolled entry of cells into the cell cycle from G0
• D Promote genomic instability by disabling DNA mismatch repair

Explanation

BCL2 is an anti-apoptotic member of the Bcl-2 family that resides in the mitochondrial outer membrane and prevents BAX/BAK-mediated permeabilization, thereby blocking cytochrome c release. In normal germinal centers BCL2 is downregulated so that non-productive B cells undergo apoptosis. The t(14;18) translocation places BCL2 under the immunoglobulin heavy chain promoter, and the resulting inhibition of apoptosis allows survival of follicular lymphoma cells. It is not a cell cycle regulator.

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.