In the WHO 2022 classification of myeloid neoplasms, which entity has been newly recognized as a distinct AML subtype defined by mutations in NPM1, and what is its biological significance?

• A AML with NPM1 mutation — classified as AML regardless of blast percentage if characteristic mutations are present ✓
• B AML with NPM1 mutation — requires ≥20% blasts and is classified as intermediate-risk only
• C AML with NPM1 mutation — can be diagnosed with ≥10% blasts and confers favorable prognosis, but only if FLT3-ITD is co-mutated
• D AML with NPM1 mutation — classified as myelodysplastic syndrome if blasts are between 10–19%

Explanation

Per the WHO 2022 classification (and the ICC 2022 consensus), AML with NPM1 mutation is defined as a distinct entity that can be diagnosed when ≥10% blasts are present (lowered from 20%), reflecting the biological distinctiveness and favorable prognosis conferred by NPM1 mutations in the absence of FLT3-ITD or adverse cytogenetics. NPM1 mutation causes cytoplasmic dislocation of nucleophosmin; when NPM1 is mutated alone, the prognosis is favorable with standard induction therapy.

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

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