A 68-year-old man has multiple myeloma. Bone marrow biopsy shows 35% plasma cells. He has serum M-protein (IgG kappa) of 4.2 g/dL, calcium 11.5 mg/dL, creatinine 2.8 mg/dL, and multiple osteolytic lesions. Which translocation most commonly found in IgH-associated myeloma and confers poor prognosis is best treated with bortezomib-containing regimens?
- A t(11;14) — overexpression of cyclin D1
- B t(4;14) — FGFR3 and MMSET overexpression ✓
- C t(14;16) — MAF transcription factor
- D del(13q) alone — intermediate risk
Explanation
t(4;14)(p16;q32) in multiple myeloma leads to overexpression of FGFR3 and MMSET (NSD2), both conferring poor prognosis. Importantly, proteasome inhibitor-based regimens (bortezomib) partially overcome the adverse prognosis conferred by t(4;14), making this translocation detection clinically actionable. t(11;14) is the most common IgH translocation in myeloma (~15-20%) but is associated with cyclin D1 overexpression and intermediate/standard prognosis; it also defines venetoclax-sensitive myeloma. t(14;16) with c-MAF activation carries very high risk. del(13q) alone is no longer considered high-risk by FISH if it is the only abnormality.
Reference: Harrison's Principles of Internal Medicine, 21st ed.
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Written and medically reviewed by the StethoPrep medical team.