Diagnostic and therapeutic pitfalls in NPM1-mutated AML: notes from the field

• Published in: Leukemia Vol. 35; no. 11; pp. 3113 - 3126
• Main Authors: Falini, Brunangelo, Sciabolacci, Sofia, Falini, Lorenza, Brunetti, Lorenzo, Martelli, Maria Paola
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 01.11.2021; Nature Publishing Group UK
• Subjects: Abnormalities; Acute myeloid leukemia; Adolescent; Aged; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biomarkers, Tumor - genetics; Cellular proteins; Criteria; Diagnosis; Female; Gene mutations; Genetic abnormalities; Genetic aspects; Health aspects; Humans; Leukemia; Leukemia research; Leukemia, Myeloid, Acute - diagnosis; Leukemia, Myeloid, Acute - drug therapy; Leukemia, Myeloid, Acute - genetics; Medical diagnosis; Middle Aged; Mutation; Myelodysplastic syndrome; Neoplasms; Nucleophosmin - genetics; Prognosis; Runx1 protein; Italy
• ISSN: 0887-6924; 1476-5551
• DOI: 10.1038/s41375-021-01222-4

Mutations of Nucleophosmin (NPM1) are the most common genetic abnormalities in adult acute myeloid leukaemia (AML), accounting for about 30% of cases. NPM1-mutated AML has been recognized as distinct entity in the 2017 World Health Organization (WHO) classification of lympho-haematopoietic neoplasms. WHO criteria allow recognition of this leukaemia entity and its distinction from AML with myelodysplasia-related changes, AML with BCR-ABL1 rearrangement and AML with RUNX1 mutations. Nevertheless, controversial issues include the percentage of blasts required for the diagnosis of NPM1-mutated AML and whether cases of NPM1-mutated myelodysplasia and chronic myelomonocytic leukaemia do exist. Evaluation of NPM1 and FLT3 status represents a major pillar of the European LeukemiaNet (ELN) genetic-based risk stratification model. Moreover, NPM1 mutations are particularly suitable for assessing measurable residual disease (MRD) since they are frequent, stable at relapse and do not drive clonal haematopoiesis. Ideally, combining monitoring of MRD with the ELN prognostication model can help to guide therapeutic decisions. Here, we provide examples of instructive cases of NPM1-mutated AML, in order to provide criteria for the appropriate diagnosis and therapy of this frequent leukaemia entity.