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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 (...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
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.
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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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