A 57-year-old man has de novo acute myeloid leukemia with a normal karyotype. Molecular testing shows a mutated NPM1 gene with wild-type FLT3 and no FLT3 internal tandem duplication. How does this molecular profile influence prognosis?

• A Prognostically irrelevant because NPM1 mutations occur only in secondary AML
• B Adverse, mandating immediate allogeneic transplant in first remission
• C Neutral, with outcome identical to unmutated NPM1 cases regardless of FLT3 status
• D Favorable, comparable to core binding factor AML ✓

Explanation

In cytogenetically normal AML, isolated NPM1 mutation (with cytoplasmic dislocation of the nucleophosmin protein) in the absence of FLT3-ITD defines a favorable-risk group with high complete remission rates, approaching outcomes seen in core binding factor leukemias. FLT3-ITD, especially with a high allelic ratio, converts NPM1-mutated disease to intermediate or adverse risk. NPM1 mutations occur in de novo as well as secondary AML, so the last option is incorrect.

Reference: Robbins and Cotran Pathologic Basis of Disease, 10th ed.

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