In follicular lymphoma, the t(14;18) translocation results in overexpression of the BCL2 protein. What is the functional consequence of this protein that drives lymphomagenesis?
- A It activates the NOTCH1 pathway, promoting survival of germinal centre cells
- B It constitutively activates the B-cell receptor through NF-kappa-B signalling
- C It blocks mitochondrial apoptosis by preventing BAX and BAK pore formation ✓
- D It degrades p53, disabling checkpoint control of DNA damage
Correct answer: C. It blocks mitochondrial apoptosis by preventing BAX and BAK pore formation
Explanation
t(14;18) places BCL2 under the IgH enhancer, so germinal centre C cells, which normally die by apoptosis if they fail affinity selection, survive indefinitely. BCL2 is an anti-apoptotic member of the BCL2 family that sequesters BH3-only proteins and prevents oligomerisation of the pro-apoptotic effectors BAX and BAK on the mitochondrial membrane. Constitutive NF-kappa-C activation is the hallmark of activated C-cell receptor signalling in ABC-type DLBCL, not follicular lymphoma.
Reference: Robbins and Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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