Chronic lymphocytic leukemia (CLL) prognosis is significantly stratified by IGHV (immunoglobulin heavy chain variable gene) mutation status. Which statement is correct?
- A Unmutated IGHV is associated with longer remission duration after fludarabine-based therapy
- B IGHV mutation status only matters in Rai stage IV disease
- C Mutated IGHV (>2% divergence from germline) is associated with favorable prognosis and longer time to treatment ✓
- D Mutated IGHV correlates with ZAP-70 positivity and CD38 overexpression
Correct answer: C. Mutated IGHV (>2% divergence from germline) is associated with favorable prognosis and longer time to treatment
Explanation
Mutated IGHV (≥2% divergence from germline, indicating antigen-experienced post-germinal center origin) defines a favorable CLL subset with indolent behavior and longer time to first treatment. Unmutated IGHV CLL originates from naive B cells, shows aggressive behavior, and is associated with ZAP-70 and CD38 positivity (surrogates for unmutated IGHV). Fludarabine-based regimens show shorter remission in unmutated IGHV despite initial responses.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
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