Frontiers in Oncology (Apr 2018)
NOTCH1 Is Aberrantly Activated in Chronic Lymphocytic Leukemia Hematopoietic Stem Cells
- Mauro Di Ianni,
- Mauro Di Ianni,
- Stefano Baldoni,
- Beatrice Del Papa,
- Patrizia Aureli,
- Erica Dorillo,
- Filomena De Falco,
- Elisa Albi,
- Emanuela Varasano,
- Ambra Di Tommaso,
- Raffaella Giancola,
- Patrizia Accorsi,
- Gianluca Rotta,
- Chiara Rompietti,
- Estevão Carlos Silva Barcelos,
- Estevão Carlos Silva Barcelos,
- Antonio Francesco Campese,
- Paolo Di Bartolomeo,
- Isabella Screpanti,
- Emanuela Rosati,
- Franca Falzetti,
- Paolo Sportoletti
Affiliations
- Mauro Di Ianni
- Department of Medicine and Aging Sciences, University of Chieti Pescara, Chieti, Italy
- Mauro Di Ianni
- Department of Hematology, Transfusion Medicine and Biotechnologies, Ospedale Civile, Pescara, Italy
- Stefano Baldoni
- Department of Life, Health and Environmental Sciences, Hematology Section, University of L’Aquila, L’Aquila, Italy
- Beatrice Del Papa
- Institute of Hematology-Centro di Ricerche Emato-Oncologiche (CREO), University of Perugia, Perugia, Italy
- Patrizia Aureli
- Institute of Hematology-Centro di Ricerche Emato-Oncologiche (CREO), University of Perugia, Perugia, Italy
- Erica Dorillo
- Institute of Hematology-Centro di Ricerche Emato-Oncologiche (CREO), University of Perugia, Perugia, Italy
- Filomena De Falco
- Institute of Hematology-Centro di Ricerche Emato-Oncologiche (CREO), University of Perugia, Perugia, Italy
- Elisa Albi
- Institute of Hematology-Centro di Ricerche Emato-Oncologiche (CREO), University of Perugia, Perugia, Italy
- Emanuela Varasano
- Institute of Hematology-Centro di Ricerche Emato-Oncologiche (CREO), University of Perugia, Perugia, Italy
- Ambra Di Tommaso
- Department of Life, Health and Environmental Sciences, Hematology Section, University of L’Aquila, L’Aquila, Italy
- Raffaella Giancola
- Department of Hematology, Transfusion Medicine and Biotechnologies, Ospedale Civile, Pescara, Italy
- Patrizia Accorsi
- Department of Hematology, Transfusion Medicine and Biotechnologies, Ospedale Civile, Pescara, Italy
- Gianluca Rotta
- BD Biosciences, San Jose, Italy
- Chiara Rompietti
- Institute of Hematology-Centro di Ricerche Emato-Oncologiche (CREO), University of Perugia, Perugia, Italy
- Estevão Carlos Silva Barcelos
- Institute of Hematology-Centro di Ricerche Emato-Oncologiche (CREO), University of Perugia, Perugia, Italy
- Estevão Carlos Silva Barcelos
- Universidade Federal do Espírito Santo, Vitória, Brazil
- Antonio Francesco Campese
- Department of Molecular Medicine, Sapienza, University of Rome, Rome, Italy
- Paolo Di Bartolomeo
- Department of Hematology, Transfusion Medicine and Biotechnologies, Ospedale Civile, Pescara, Italy
- Isabella Screpanti
- Department of Molecular Medicine, Sapienza, University of Rome, Rome, Italy
- Emanuela Rosati
- Department of Experimental Medicine, Biosciences and Medical Embriology Section, University of Perugia, Perugia, Italy
- Franca Falzetti
- Institute of Hematology-Centro di Ricerche Emato-Oncologiche (CREO), University of Perugia, Perugia, Italy
- Paolo Sportoletti
- Institute of Hematology-Centro di Ricerche Emato-Oncologiche (CREO), University of Perugia, Perugia, Italy
- DOI
- https://doi.org/10.3389/fonc.2018.00105
- Journal volume & issue
-
Vol. 8
Abstract
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.
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