A 62-year-old woman presents with painless generalized lymphadenopathy. Lymph node biopsy shows a nodular proliferation of centrocytes with a t(14;18) translocation. The anti-apoptotic effect of this translocation results from which molecular event?

• A Amplification of the BCL2 locus on chromosome 18
• B Formation of a BCL2-MYC fusion protein with constitutive transcriptional activity
• C Deletion of the BH3 domain of BCL2, converting it into a dominant-negative inhibitor
• D Overexpression of BCL2 driven by juxtaposition to the immunoglobulin heavy chain promoter ✓

Explanation

In follicular lymphoma, t(14;18)(q21;q32) places the BCL2 gene next to the immunoglobulin heavy chain locus enhancer on chromosome 14, causing constitutive overexpression of the anti-apoptotic BCL2 protein. This blocks cytochrome c release and allows survival of cells that should die. There is no fusion protein formed, no BH3 deletion, and the mechanism is dysregulated expression rather than gene amplification.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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