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NOTCH1 Is Aberrantly Activated in Chronic Lymphocytic Leukemia Hematopoietic Stem Cells
To investigate chronic lymphocytic leukemia (CLL)-initiating cells, we assessed NOTCH1 mutation/expression in hematopoietic stem cells (HSCs). In NOTCH1-mutated CLL, we detected subclonal mutations in 57% CD34+/CD38− HSCs. NOTCH1 mutation was present in 66% CD34+/CD38+ progenitor cells displaying an...
| Autores principales: | , , , , , , , , , , , , , , , , , , , |
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| Formato: | Online Artículo Texto |
| Lenguaje: | English |
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Frontiers Media S.A.
2018
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| Materias: | |
| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5919960/ https://www.ncbi.nlm.nih.gov/pubmed/29732315 http://dx.doi.org/10.3389/fonc.2018.00105 |
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| author | Di Ianni, Mauro Baldoni, Stefano Del Papa, Beatrice Aureli, Patrizia Dorillo, Erica De Falco, Filomena Albi, Elisa Varasano, Emanuela Di Tommaso, Ambra Giancola, Raffaella Accorsi, Patrizia Rotta, Gianluca Rompietti, Chiara Silva Barcelos, Estevão Carlos Campese, Antonio Francesco Di Bartolomeo, Paolo Screpanti, Isabella Rosati, Emanuela Falzetti, Franca Sportoletti, Paolo |
| author_facet | Di Ianni, Mauro Baldoni, Stefano Del Papa, Beatrice Aureli, Patrizia Dorillo, Erica De Falco, Filomena Albi, Elisa Varasano, Emanuela Di Tommaso, Ambra Giancola, Raffaella Accorsi, Patrizia Rotta, Gianluca Rompietti, Chiara Silva Barcelos, Estevão Carlos Campese, Antonio Francesco Di Bartolomeo, Paolo Screpanti, Isabella Rosati, Emanuela Falzetti, Franca Sportoletti, Paolo |
| author_sort | Di Ianni, Mauro |
| collection | PubMed |
| description | To investigate chronic lymphocytic leukemia (CLL)-initiating cells, we assessed NOTCH1 mutation/expression in hematopoietic stem cells (HSCs). In NOTCH1-mutated CLL, we detected subclonal mutations in 57% CD34+/CD38− HSCs. NOTCH1 mutation was present in 66% CD34+/CD38+ progenitor cells displaying an increased mutational burden compared to HSCs. Flow cytometric analysis revealed significantly higher NOTCH1 activation in CD34+/CD38− and CD34+/CD38+ cells from CLL patients, regardless NOTCH1 mutation compared to healthy donors. Activated NOTCH1 resulted in overexpression of the NOTCH1 target c-MYC. We conclude that activated NOTCH1 is an early event in CLL that may contribute to aberrant HSCs in this disease. |
| format | Online Article Text |
| id | pubmed-5919960 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2018 |
| publisher | Frontiers Media S.A. |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-59199602018-05-04 NOTCH1 Is Aberrantly Activated in Chronic Lymphocytic Leukemia Hematopoietic Stem Cells Di Ianni, Mauro Baldoni, Stefano Del Papa, Beatrice Aureli, Patrizia Dorillo, Erica De Falco, Filomena Albi, Elisa Varasano, Emanuela Di Tommaso, Ambra Giancola, Raffaella Accorsi, Patrizia Rotta, Gianluca Rompietti, Chiara Silva Barcelos, Estevão Carlos Campese, Antonio Francesco Di Bartolomeo, Paolo Screpanti, Isabella Rosati, Emanuela Falzetti, Franca Sportoletti, Paolo Front Oncol Oncology To investigate chronic lymphocytic leukemia (CLL)-initiating cells, we assessed NOTCH1 mutation/expression in hematopoietic stem cells (HSCs). In NOTCH1-mutated CLL, we detected subclonal mutations in 57% CD34+/CD38− HSCs. NOTCH1 mutation was present in 66% CD34+/CD38+ progenitor cells displaying an increased mutational burden compared to HSCs. Flow cytometric analysis revealed significantly higher NOTCH1 activation in CD34+/CD38− and CD34+/CD38+ cells from CLL patients, regardless NOTCH1 mutation compared to healthy donors. Activated NOTCH1 resulted in overexpression of the NOTCH1 target c-MYC. We conclude that activated NOTCH1 is an early event in CLL that may contribute to aberrant HSCs in this disease. Frontiers Media S.A. 2018-04-20 /pmc/articles/PMC5919960/ /pubmed/29732315 http://dx.doi.org/10.3389/fonc.2018.00105 Text en Copyright © 2018 Di Ianni, Baldoni, Del Papa, Aureli, Dorillo, De Falco, Albi, Varasano, Di Tommaso, Giancola, Accorsi, Rotta, Rompietti, Silva Barcelos, Campese, Di Bartolomeo, Screpanti, Rosati, Falzetti and Sportoletti. 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 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 Di Ianni, Mauro Baldoni, Stefano Del Papa, Beatrice Aureli, Patrizia Dorillo, Erica De Falco, Filomena Albi, Elisa Varasano, Emanuela Di Tommaso, Ambra Giancola, Raffaella Accorsi, Patrizia Rotta, Gianluca Rompietti, Chiara Silva Barcelos, Estevão Carlos Campese, Antonio Francesco Di Bartolomeo, Paolo Screpanti, Isabella Rosati, Emanuela Falzetti, Franca Sportoletti, Paolo NOTCH1 Is Aberrantly Activated in Chronic Lymphocytic Leukemia Hematopoietic Stem Cells |
| title | NOTCH1 Is Aberrantly Activated in Chronic Lymphocytic Leukemia Hematopoietic Stem Cells |
| title_full | NOTCH1 Is Aberrantly Activated in Chronic Lymphocytic Leukemia Hematopoietic Stem Cells |
| title_fullStr | NOTCH1 Is Aberrantly Activated in Chronic Lymphocytic Leukemia Hematopoietic Stem Cells |
| title_full_unstemmed | NOTCH1 Is Aberrantly Activated in Chronic Lymphocytic Leukemia Hematopoietic Stem Cells |
| title_short | NOTCH1 Is Aberrantly Activated in Chronic Lymphocytic Leukemia Hematopoietic Stem Cells |
| title_sort | notch1 is aberrantly activated in chronic lymphocytic leukemia hematopoietic stem cells |
| topic | Oncology |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5919960/ https://www.ncbi.nlm.nih.gov/pubmed/29732315 http://dx.doi.org/10.3389/fonc.2018.00105 |
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