A 68-year-old man with IgG kappa myeloma undergoes bone marrow biopsy after initial treatment. Cytogenetics reveal del(17p13). Which downstream molecular pathway is primarily disrupted by this deletion, and how does this influence prognosis?
- A Del(17p13) deletes RB1, disrupting G1/S cell cycle checkpoint; it confers intermediate risk requiring no change in treatment strategy
- B Del(17p13) deletes TP53, abrogating the apoptotic response to DNA damage; it confers high-risk disease with poor response to conventional melphalan-based therapy and mandate bortezomib-based regimens ✓
- C Del(17p13) deletes BRCA1, impairing homologous recombination repair; PARP inhibitors are first-line treatment
- D Del(17p13) activates the NF-κB pathway by losing an inhibitory locus; anti-NF-κB therapy is curative
Correct answer: B. Del(17p13) deletes TP53, abrogating the apoptotic response to DNA damage; it confers high-risk disease with poor response to conventional melphalan-based therapy and mandate bortezomib-based regimens
Explanation
Del(17p13) in multiple myeloma deletes the TP53 locus, eliminating p53-mediated apoptosis in response to DNA damage. This is one of the highest-risk cytogenetic lesions in myeloma, associated with short progression-free survival and overall survival with conventional therapy. Bortezomib-based induction regimens provide superior outcomes in del(17p) myeloma compared to non-proteasome-inhibitor regimens. The deletion does not primarily target RB1, BRCA1, or an NF-κB inhibitory locus at 17p.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.