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High Throughput Molecular Characterization of Normal Karyotype Acute Myeloid Leukemia in the Context of the Prospective Trial 02/06 of the Northern Italy Leukemia Group (NILG)

Silvia Salmoiraghi, Roberta Cavagna, Pamela Zanghì, Chiara Pavoni, Anna Michelato, Ksenija Buklijas, Lara Elidi, Tamara Intermesoli, Federico Lussana, Elena Oldani, Chiara Caprioli, Paola Stefanoni (+17 others)
2020 Cancers  

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By way of a Next-Generation Sequencing NGS high throughput approach, we defined the mutational profile in a cohort of 221 normal karyotype acute myeloid leukemia (NK-AML) enrolled into a prospective randomized clinical trial, designed to evaluate an intensified chemotherapy program for remission induction. NPM1, DNMT3A, and FLT3-ITD were the most frequently mutated genes while DNMT3A, FLT3, IDH1, PTPN11, and RAD21 mutations were more common in the NPM1 mutated patients (p < 0.05). IDH1 R132H
more » ... ation was strictly associated with NPM1 mutation and mutually exclusive with RUNX1 and ASXL1. In the whole cohort of NK-AML, no matter the induction chemotherapy used, by multivariate analysis, the achievement of complete remission was negatively affected by the SRSF2 mutation. Alterations of FLT3 (FLT3-ITD) and U2AF1 were associated with a worse overall and disease-free survival (p < 0.05). FLT3-ITD positive patients who proceeded to alloHSCT had a survival probability similar to FLT3-ITD negative patients and the transplant outcome was no different when comparing high and low-AR-FLT3-ITD subgroups in terms of both OS and DFS. In conclusion, a comprehensive molecular profile for NK-AML allows for the identification of genetic lesions associated to different clinical outcomes and the selection of the most appropriate and effective treatment strategies, including stem cell transplantation and targeted therapies.
doi:10.3390/cancers12082242 pmid:32796597 fatcat:txxxw3o3h5dyxiywml3goyyehe
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Silvia Salmoiraghi, Roberta Cavagna, Pamela Zanghì, Chiara Pavoni, Anna Michelato, Ksenija Buklijas, Lara Elidi, Tamara Intermesoli, Federico Lussana, Elena Oldani, Chiara Caprioli, Paola Stefanoni, Giacomo Gianfaldoni, Ernesta Audisio, Elisabetta Terruzzi, Lorella De Paoli, Erika Borlenghi, Irene Cavattoni, Daniele Mattei, Annamaria Scattolin, Monica Tajana, Fabio Ciceri, Elisabetta Todisco, Leonardo Campiotti, Paolo Corradini, Nicola Fracchiolla, Renato Bassan, Alessandro Rambaldi, Orietta Spinelli. "High Throughput Molecular Characterization of Normal Karyotype Acute Myeloid Leukemia in the Context of the Prospective Trial 02/06 of the Northern Italy Leukemia Group (NILG)." Cancers 12.8 (2020) 2242