A 65-year-old woman has recurrent infections, peripheral blood showing 40,000 mature-appearing small lymphocytes, and positive Coombs test with hemolytic anemia. Flow cytometry shows CD5+, CD19+, CD23+, CD10- surface immunoglobulin dim. The most likely diagnosis is chronic lymphocytic leukemia (CLL). Which genetic abnormality in CLL is associated with the worst prognosis?
- A del(17p) — TP53 deletion ✓
- B del(13q14) — isolated
- C Trisomy 12
- D del(11q) — ATM deletion
Correct answer: A. del(17p) — TP53 deletion
Explanation
In CLL, del(17p) resulting in TP53 loss confers the worst prognosis due to chemoimmunotherapy resistance; patients often require targeted agents (ibrutinib, venetoclax) as frontline therapy. The hierarchical prognostic order by FISH is: del(17p) > del(11q) > trisomy 12 > normal > del(13q14) isolated (best prognosis). Del(13q14) as the sole abnormality is associated with indolent disease and the best outcome among these cytogenetic categories.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
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Written and medically reviewed by the StethoPrep medical team.