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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...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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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. |
format | Online Article Text |
id | pubmed-7464263 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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