Npm1‐mutated myeloid neoplasms with <20% blasts: A really distinct clinico‐pathologic entity?

Fabio Forghieri, Vincenzo Nasillo, Ambra Paolini, Francesca Bettelli, Valeria Pioli, Davide Giusti, Andrea Gilioli, Corrado Colasante, Gloria Acquaviva, Giovanni Riva, Patrizia Barozzi, Rossana Maffei, Leonardo Potenza, Roberto Marasca, Claudio Fozza, Enrico Tagliafico, Tommaso Trenti, Patrizia Comoli, Giuseppe Longo, Mario Luppi

Research output: Contribution to journalReview articlepeer-review


Nucleophosmin (NPM1) gene mutations rarely occur in non‐acute myeloid neoplasms (MNs) with <20% blasts. Among nearly 10,000 patients investigated so far, molecular analyses documented NPM1 mutations in around 2% of myelodysplastic syndrome (MDS) cases, mainly belonging to MDS with excess of blasts, and 3% of myelodysplastic/myeloproliferative neoplasm (MDS/MPN) cases, prevalently classified as chronic myelomonocytic leukemia. These uncommon malignancies are associated with an aggressive clinical course, relatively rapid progression to overt acute myeloid leukemia (AML) and poor survival outcomes, raising controversies on their classification as distinct clinico‐pathologic entities. Furthermore, fit patients with NPM1‐mutated MNs with <20% blasts could benefit most from upfront intensive chemotherapy for AML rather than from moderate intensity MDS‐directed therapies, although no firm conclusion can currently be drawn on best therapeutic approaches, due to the limited available data, obtained from small and mainly retrospective series. Caution is also suggested in definitely diagnosing NPM1‐mutated MNs with blast count <20%, since NPM1‐mutated AML cases frequently present dysplastic features and multilineage bone marrow cells showing abnormal cytoplasmic NPM1 protein delocalization by immunohistochemical staining, therefore belonging to NPM1‐mutated clone regardless of blast morphology. Further prospective studies are warranted to definitely assess whether NPM1 mutations may become sufficient to diagnose AML, irrespective of blast percentage.

Original languageEnglish
Article number8975
Pages (from-to)1-27
Number of pages27
JournalInternational Journal of Molecular Sciences
Issue number23
Publication statusPublished - Dec 1 2020


  • Acute myeloid leukemia
  • Chronic myelomonocytic leukemia
  • Leukemogenesis
  • Myelodysplastic syndromes
  • Myelodysplastic/myeloproliferative neoplasms
  • NPM1 mutation

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry


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