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Gianfranco Catalano
Pasquale Niscola
Cristina Banella
Daniela Diverio
Malgorzata Monika Trawinska
Stefano Fratoni
Rita Iazzoni
Paolo de Fabritiis
Elisabetta abruzzese
Nelida Ines Noguera


NPM1, AML with BCR-ABL1, CML-BP, TKI therapy


Break point cluster region - Abelson (BCR-ABL1) chimeric protein and mutated Nucleophosmin (NPM1) are often present in hematological cancers, but they rarely coexist in the same disease. Both anomalies are considered founder mutations causing inhibition of differentiation and apoptosis, but BCR-ABL1 could act as a secondary mutation conferring a proliferative advantage to a pre-neoplastic clone. The 2016 World Health Organization (WHO) classification lists the provisional acute myeloid leukemia (AML) with BCR-ABL1, which must be diagnosed differentially from the rare blast phase (BP) onset of a chronic myeloid leukemia (CML), mainly because of the different therapeutic approach in the use of tyrosine kinase inhibitors (TKI). Here we review all published cases since 1975 and describe a case from our institution in order to discuss the clinical and molecular features of this rare combination, and report the latest acquisition about an occurrence that could pertain either to the rare AML BCR-ABL1 positive or the even rarer CML-BP with mutated NPM1 at onset.


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