2  Myeloid Mutations in AML

3 NPM1

3.1 Pathologic Findings

• NPM1 mut AML is associated with cytoplasmic staining, cup- nuclei, dysplasia, monocytic phenotype, CD34 negativity, normal karyotype, co-mutations in FLT3, DNMT3A, or IDH1/2, and extramedullary disease.

3.2 Prognosis

• Per ELN 2022 criteria, NPM1 mut/FLT3-ITD–negative AML is considered favorable risk, NPM1 mut/FLT3-ITD–positive AML is considered intermediate risk, and NPM1 mut/adverse karyotype is considered adverse risk.

• Co-mutations with WT1 or with both FLT3-ITD/DNMT3A (triple mutant) impart an adverse prognosis. Conversely, prior chemotherapy exposure and dysplasia

3.3 Treatment Algorithm