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Case Report: A Novel Activating FLT3 Mutation in Acute Myeloid Leukemia
FMS-like tyrosine kinase 3 (FLT3) is among the most common driver genes recurrently mutated in acute myeloid leukemia (AML), accounting for approximately 30% of cases. Activating mutations of the FLT3 receptor include internal tandem duplications (ITD) that map to the auto-inhibitory juxtamembrane (...
Autores principales: | , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8514815/ https://www.ncbi.nlm.nih.gov/pubmed/34660293 http://dx.doi.org/10.3389/fonc.2021.728613 |
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author | Bruno, Samantha Bandini, Lorenza Patuelli, Agnese Robustelli, Valentina Venturi, Claudia Mancini, Manuela Forte, Dorian De Santis, Sara Monaldi, Cecilia Grassi, Alessandra Chiurumbolo, Gabriella Paolini, Stefania Cristiano, Gianluca Papayannidis, Cristina Sartor, Chiara Nanni, Jacopo Ottaviani, Emanuela Curti, Antonio Cavo, Michele Soverini, Simona |
author_facet | Bruno, Samantha Bandini, Lorenza Patuelli, Agnese Robustelli, Valentina Venturi, Claudia Mancini, Manuela Forte, Dorian De Santis, Sara Monaldi, Cecilia Grassi, Alessandra Chiurumbolo, Gabriella Paolini, Stefania Cristiano, Gianluca Papayannidis, Cristina Sartor, Chiara Nanni, Jacopo Ottaviani, Emanuela Curti, Antonio Cavo, Michele Soverini, Simona |
author_sort | Bruno, Samantha |
collection | PubMed |
description | FMS-like tyrosine kinase 3 (FLT3) is among the most common driver genes recurrently mutated in acute myeloid leukemia (AML), accounting for approximately 30% of cases. Activating mutations of the FLT3 receptor include internal tandem duplications (ITD) that map to the auto-inhibitory juxtamembrane (JM) domain or point mutations within the tyrosine kinase domain (TKD). Several FLT3 tyrosine kinase inhibitors have been developed in the last few years, but midostaurin is currently the only one approved for the treatment of newly diagnosed patients harboring FLT3 mutations. Here we describe for the first time a novel in-frame deletion in exon 14 (JM domain) of the FLT3 gene, that we identified in a young woman with CBFb-MYH11-positive AML. We demonstrated that this novel FLT3 variant is pathogenic, since it is responsible for constitutive activation of FLT3 receptor. Finally, ex-vivo studies demonstrated that this novel mutation is sensitive to midostaurin. |
format | Online Article Text |
id | pubmed-8514815 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-85148152021-10-15 Case Report: A Novel Activating FLT3 Mutation in Acute Myeloid Leukemia Bruno, Samantha Bandini, Lorenza Patuelli, Agnese Robustelli, Valentina Venturi, Claudia Mancini, Manuela Forte, Dorian De Santis, Sara Monaldi, Cecilia Grassi, Alessandra Chiurumbolo, Gabriella Paolini, Stefania Cristiano, Gianluca Papayannidis, Cristina Sartor, Chiara Nanni, Jacopo Ottaviani, Emanuela Curti, Antonio Cavo, Michele Soverini, Simona Front Oncol Oncology FMS-like tyrosine kinase 3 (FLT3) is among the most common driver genes recurrently mutated in acute myeloid leukemia (AML), accounting for approximately 30% of cases. Activating mutations of the FLT3 receptor include internal tandem duplications (ITD) that map to the auto-inhibitory juxtamembrane (JM) domain or point mutations within the tyrosine kinase domain (TKD). Several FLT3 tyrosine kinase inhibitors have been developed in the last few years, but midostaurin is currently the only one approved for the treatment of newly diagnosed patients harboring FLT3 mutations. Here we describe for the first time a novel in-frame deletion in exon 14 (JM domain) of the FLT3 gene, that we identified in a young woman with CBFb-MYH11-positive AML. We demonstrated that this novel FLT3 variant is pathogenic, since it is responsible for constitutive activation of FLT3 receptor. Finally, ex-vivo studies demonstrated that this novel mutation is sensitive to midostaurin. Frontiers Media S.A. 2021-09-30 /pmc/articles/PMC8514815/ /pubmed/34660293 http://dx.doi.org/10.3389/fonc.2021.728613 Text en Copyright © 2021 Bruno, Bandini, Patuelli, Robustelli, Venturi, Mancini, Forte, De Santis, Monaldi, Grassi, Chiurumbolo, Paolini, Cristiano, Papayannidis, Sartor, Nanni, Ottaviani, Curti, Cavo and Soverini https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Oncology Bruno, Samantha Bandini, Lorenza Patuelli, Agnese Robustelli, Valentina Venturi, Claudia Mancini, Manuela Forte, Dorian De Santis, Sara Monaldi, Cecilia Grassi, Alessandra Chiurumbolo, Gabriella Paolini, Stefania Cristiano, Gianluca Papayannidis, Cristina Sartor, Chiara Nanni, Jacopo Ottaviani, Emanuela Curti, Antonio Cavo, Michele Soverini, Simona Case Report: A Novel Activating FLT3 Mutation in Acute Myeloid Leukemia |
title | Case Report: A Novel Activating FLT3 Mutation in Acute Myeloid Leukemia |
title_full | Case Report: A Novel Activating FLT3 Mutation in Acute Myeloid Leukemia |
title_fullStr | Case Report: A Novel Activating FLT3 Mutation in Acute Myeloid Leukemia |
title_full_unstemmed | Case Report: A Novel Activating FLT3 Mutation in Acute Myeloid Leukemia |
title_short | Case Report: A Novel Activating FLT3 Mutation in Acute Myeloid Leukemia |
title_sort | case report: a novel activating flt3 mutation in acute myeloid leukemia |
topic | Oncology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8514815/ https://www.ncbi.nlm.nih.gov/pubmed/34660293 http://dx.doi.org/10.3389/fonc.2021.728613 |
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