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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)

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 ind...

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Autores principales: Salmoiraghi, Silvia, Cavagna, Roberta, Zanghì, Pamela, Pavoni, Chiara, Michelato, Anna, Buklijas, Ksenija, Elidi, Lara, Intermesoli, Tamara, Lussana, Federico, Oldani, Elena, Caprioli, Chiara, Stefanoni, Paola, Gianfaldoni, Giacomo, Audisio, Ernesta, Terruzzi, Elisabetta, De Paoli, Lorella, Borlenghi, Erika, Cavattoni, Irene, Mattei, Daniele, Scattolin, Annamaria, Tajana, Monica, Ciceri, Fabio, Todisco, Elisabetta, Campiotti, Leonardo, Corradini, Paolo, Fracchiolla, Nicola, Bassan, Renato, Rambaldi, Alessandro, Spinelli, Orietta
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7464263/
https://www.ncbi.nlm.nih.gov/pubmed/32796597
http://dx.doi.org/10.3390/cancers12082242
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author Salmoiraghi, Silvia
Cavagna, Roberta
Zanghì, Pamela
Pavoni, Chiara
Michelato, Anna
Buklijas, Ksenija
Elidi, Lara
Intermesoli, Tamara
Lussana, Federico
Oldani, Elena
Caprioli, Chiara
Stefanoni, Paola
Gianfaldoni, Giacomo
Audisio, Ernesta
Terruzzi, Elisabetta
De Paoli, Lorella
Borlenghi, Erika
Cavattoni, Irene
Mattei, Daniele
Scattolin, Annamaria
Tajana, Monica
Ciceri, Fabio
Todisco, Elisabetta
Campiotti, Leonardo
Corradini, Paolo
Fracchiolla, Nicola
Bassan, Renato
Rambaldi, Alessandro
Spinelli, Orietta
author_facet Salmoiraghi, Silvia
Cavagna, Roberta
Zanghì, Pamela
Pavoni, Chiara
Michelato, Anna
Buklijas, Ksenija
Elidi, Lara
Intermesoli, Tamara
Lussana, Federico
Oldani, Elena
Caprioli, Chiara
Stefanoni, Paola
Gianfaldoni, Giacomo
Audisio, Ernesta
Terruzzi, Elisabetta
De Paoli, Lorella
Borlenghi, Erika
Cavattoni, Irene
Mattei, Daniele
Scattolin, Annamaria
Tajana, Monica
Ciceri, Fabio
Todisco, Elisabetta
Campiotti, Leonardo
Corradini, Paolo
Fracchiolla, Nicola
Bassan, Renato
Rambaldi, Alessandro
Spinelli, Orietta
author_sort Salmoiraghi, Silvia
collection PubMed
description 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 mutation 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.
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spelling pubmed-74642632020-09-04 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) Salmoiraghi, Silvia Cavagna, Roberta Zanghì, Pamela Pavoni, Chiara Michelato, Anna Buklijas, Ksenija Elidi, Lara Intermesoli, Tamara Lussana, Federico Oldani, Elena Caprioli, Chiara Stefanoni, Paola Gianfaldoni, Giacomo Audisio, Ernesta Terruzzi, Elisabetta De Paoli, Lorella Borlenghi, Erika Cavattoni, Irene Mattei, Daniele Scattolin, Annamaria Tajana, Monica Ciceri, Fabio Todisco, Elisabetta Campiotti, Leonardo Corradini, Paolo Fracchiolla, Nicola Bassan, Renato Rambaldi, Alessandro Spinelli, Orietta Cancers (Basel) Article 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 mutation 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. MDPI 2020-08-11 /pmc/articles/PMC7464263/ /pubmed/32796597 http://dx.doi.org/10.3390/cancers12082242 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Salmoiraghi, Silvia
Cavagna, Roberta
Zanghì, Pamela
Pavoni, Chiara
Michelato, Anna
Buklijas, Ksenija
Elidi, Lara
Intermesoli, Tamara
Lussana, Federico
Oldani, Elena
Caprioli, Chiara
Stefanoni, Paola
Gianfaldoni, Giacomo
Audisio, Ernesta
Terruzzi, Elisabetta
De Paoli, Lorella
Borlenghi, Erika
Cavattoni, Irene
Mattei, Daniele
Scattolin, Annamaria
Tajana, Monica
Ciceri, Fabio
Todisco, Elisabetta
Campiotti, Leonardo
Corradini, Paolo
Fracchiolla, Nicola
Bassan, Renato
Rambaldi, Alessandro
Spinelli, Orietta
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)
title 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)
title_full 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)
title_fullStr 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)
title_full_unstemmed 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)
title_short 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)
title_sort 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)
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7464263/
https://www.ncbi.nlm.nih.gov/pubmed/32796597
http://dx.doi.org/10.3390/cancers12082242
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