TY - JOUR
T1 - Npm1‐mutated myeloid neoplasms with <20% blasts
T2 - A really distinct clinico‐pathologic entity?
AU - Forghieri, Fabio
AU - Nasillo, Vincenzo
AU - Paolini, Ambra
AU - Bettelli, Francesca
AU - Pioli, Valeria
AU - Giusti, Davide
AU - Gilioli, Andrea
AU - Colasante, Corrado
AU - Acquaviva, Gloria
AU - Riva, Giovanni
AU - Barozzi, Patrizia
AU - Maffei, Rossana
AU - Potenza, Leonardo
AU - Marasca, Roberto
AU - Fozza, Claudio
AU - Tagliafico, Enrico
AU - Trenti, Tommaso
AU - Comoli, Patrizia
AU - Longo, Giuseppe
AU - Luppi, Mario
N1 - Funding Information:
This work was supported by grants from the Associazione Italiana per la Ricerca sul Cancro (AIRC), Milan, Italy (IG 20624?2018) (ML), the Progetto di Eccellenza Dipartimento MIUR 2017 (ML), and the ?Charity Dinner initiative? in memory of Alberto Fontana for Associazione Italiana Lotta alle Leucemie, Linfoma e Mieloma (AIL)?Sezione ?Luciano Pavarotti??Modena?ONLUS. This work was also supported by grants from the Fondazione Regionale per la Ricerca Biomedica (PC); Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Policlinico San Matteo di Pavia [Ricerca Corrente 08069113 and 08069119 (PC)]; Fondazione Just Italia (PC).
Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/12/1
Y1 - 2020/12/1
N2 - 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.
AB - 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.
KW - Acute myeloid leukemia
KW - Chronic myelomonocytic leukemia
KW - Leukemogenesis
KW - Myelodysplastic syndromes
KW - Myelodysplastic/myeloproliferative neoplasms
KW - NPM1 mutation
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U2 - 10.3390/ijms21238975
DO - 10.3390/ijms21238975
M3 - Review article
AN - SCOPUS:85096638130
VL - 21
SP - 1
EP - 27
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
SN - 1661-6596
IS - 23
M1 - 8975
ER -