TY - JOUR AU - Di Ianni, Mauro AU - Baldoni, Stefano AU - Del Papa, Beatrice AU - Aureli, Patrizia AU - Dorillo, Erica AU - De Falco, Filomena AU - Albi, Elisa AU - Varasano, Emanuela AU - Di Tommaso, Ambra AU - Giancola, Raffaella AU - Accorsi, Patrizia AU - Rotta, Gianluca AU - Rompietti, Chiara AU - Silva Barcelos, Estevão Carlos AU - Campese, Antonio Francesco AU - Di Bartolomeo, Paolo AU - Screpanti, Isabella AU - Rosati, Emanuela AU - Falzetti, Franca AU - Sportoletti, Paolo PY - 2018 M3 - Original Research TI - NOTCH1 Is Aberrantly Activated in Chronic Lymphocytic Leukemia Hematopoietic Stem Cells JO - Frontiers in Oncology UR - https://www.frontiersin.org/articles/10.3389/fonc.2018.00105 VL - 8 SN - 2234-943X N2 - 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. ER -