A 60-year-old man has de novo acute myeloid leukaemia with a normal karyotype. Molecular testing reveals a mutated NPM1 together with an internal tandem duplication of FLT3. How does this combined genotype affect risk stratification?
- A Intermediate risk, because FLT3-ITD negates the favourable effect of NPM1 mutation ✓
- B Favourable risk despite normal cytogenetics
- C Favourable risk only if the patient is under 40 years
- D Irrelevant to prognosis once the karyotype is normal
Correct answer: A. Intermediate risk, because FLT3-ITD negates the favourable effect of NPM1 mutation
Explanation
In cytogenetically normal AML, isolated NPM1 mutation predicts a favourable outcome, while FLT3-ITD confers a high relapse risk by constitutively activating FLT3 signalling. When both mutations coexist, the adverse impact of FLT3-ITD largely overrides the benefit of NPM1, placing the patient in the intermediate or adverse category depending on ITD allele burden. Age thresholds do not modify this molecular risk assignment.
Reference: Robbins and Cotran Pathologic Basis of Disease, 10th ed.
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