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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.
Affiliation
  • Di Ianni M; Department of Medicine and Aging Sciences, University of Chieti Pescara, Chieti, Italy.
  • Baldoni S; Department of Hematology, Transfusion Medicine and Biotechnologies, Ospedale Civile, Pescara, Italy.
  • Del Papa B; Department of Life, Health and Environmental Sciences, Hematology Section, University of L'Aquila, L'Aquila, Italy.
  • Aureli P; Institute of Hematology-Centro di Ricerche Emato-Oncologiche (CREO), University of Perugia, Perugia, Italy.
  • Dorillo E; Institute of Hematology-Centro di Ricerche Emato-Oncologiche (CREO), University of Perugia, Perugia, Italy.
  • De Falco F; Institute of Hematology-Centro di Ricerche Emato-Oncologiche (CREO), University of Perugia, Perugia, Italy.
  • Albi E; Institute of Hematology-Centro di Ricerche Emato-Oncologiche (CREO), University of Perugia, Perugia, Italy.
  • Varasano E; Institute of Hematology-Centro di Ricerche Emato-Oncologiche (CREO), University of Perugia, Perugia, Italy.
  • Di Tommaso A; Institute of Hematology-Centro di Ricerche Emato-Oncologiche (CREO), University of Perugia, Perugia, Italy.
  • Giancola R; Department of Life, Health and Environmental Sciences, Hematology Section, University of L'Aquila, L'Aquila, Italy.
  • Accorsi P; Department of Hematology, Transfusion Medicine and Biotechnologies, Ospedale Civile, Pescara, Italy.
  • Rotta G; Department of Hematology, Transfusion Medicine and Biotechnologies, Ospedale Civile, Pescara, Italy.
  • Rompietti C; BD Biosciences, San Jose, Italy.
  • Silva Barcelos EC; Institute of Hematology-Centro di Ricerche Emato-Oncologiche (CREO), University of Perugia, Perugia, Italy.
  • Campese AF; Institute of Hematology-Centro di Ricerche Emato-Oncologiche (CREO), University of Perugia, Perugia, Italy.
  • Di Bartolomeo P; Universidade Federal do Espírito Santo, Vitória, Brazil.
  • Screpanti I; Department of Molecular Medicine, Sapienza, University of Rome, Rome, Italy.
  • Rosati E; Department of Hematology, Transfusion Medicine and Biotechnologies, Ospedale Civile, Pescara, Italy.
  • Falzetti F; Department of Molecular Medicine, Sapienza, University of Rome, Rome, Italy.
  • Sportoletti P; Department of Experimental Medicine, Biosciences and Medical Embriology Section, University of Perugia, Perugia, Italy.
Front Oncol ; 8: 105, 2018.
Article in En | MEDLINE | ID: mdl-29732315
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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Full text: 1 Collection: 01-internacional Database: MEDLINE Language: En Journal: Front Oncol Year: 2018 Document type: Article Affiliation country: Italy Country of publication: Switzerland
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Full text: 1 Collection: 01-internacional Database: MEDLINE Language: En Journal: Front Oncol Year: 2018 Document type: Article Affiliation country: Italy Country of publication: Switzerland