Jessica Petiti: Division of Advanced Materials Metrology and Life Sciences, Istituto Nazionale di Ricerca Metrologica (INRiM), 10135 Turin, Italy. ORCID
Ymera Pignochino: Department of Clinical and Biological Sciences, University of Turin, 10043 Orbassano, Italy. ORCID
Aurora Schiavon: Department of Clinical and Biological Sciences, University of Turin, 10043 Orbassano, Italy. ORCID
Emilia Giugliano: Clinical and Microbiological Analysis Laboratory, San Luigi Gonzaga Hospital, 10043 Orbassano, Italy.
Enrico Berrino: Candiolo Cancer Institute, FPO-IRCCS, 10060 Candiolo, Italy.
Giorgia Giordano: Candiolo Cancer Institute, FPO-IRCCS, 10060 Candiolo, Italy.
Federico Itri: Department of Clinical and Biological Sciences, University of Turin, 10043 Orbassano, Italy. ORCID
Matteo Dragani: Division of Hematology and Cellular Therapies, San Martino Hospital, IRCCS, 16132 Genova, Italy.
Daniela Cilloni: Department of Clinical and Biological Sciences, University of Turin, 10043 Orbassano, Italy. ORCID
Marco Lo Iacono: Department of Clinical and Biological Sciences, University of Turin, 10043 Orbassano, Italy. ORCID
Acute myeloid leukemia (AML) is a complex hematologic malignancy with high morbidity and mortality. Nucleophosmin 1 (NPM1) mutations occur in approximately 30% of AML cases, and NPM1-mutated AML is classified as a distinct entity. NPM1-mutated AML patients without additional genetic abnormalities have a favorable prognosis. Despite this, 30-50% of them experience relapse. This study aimed to investigate the potential of total RNAseq in improving the characterization of NPM1-mutated AML patients. We explored genetic variations independently of myeloid stratification, revealing a complex molecular scenario. We showed that total RNAseq enables the uncovering of different genetic alterations and clonal subtypes, allowing for a comprehensive evaluation of the real expression of exome transcripts in leukemic clones and the identification of aberrant fusion transcripts. This characterization may enhance understanding and guide improved treatment strategies for NPM1mut AML patients, contributing to better outcomes. Our findings underscore the complexity of NPM1-mutated AML, supporting the incorporation of advanced technologies for precise risk stratification and personalized therapeutic strategies. The study provides a foundation for future investigations into the clinical implications of identified genetic variations and highlights the importance of evolving diagnostic approaches in leukemia management.
