table_1_NOTCH1 Is Aberrantly Activated in Chronic Lymphocytic Leukemia Hematopoietic Stem Cells.PDF (113.34 kB)

table_1_NOTCH1 Is Aberrantly Activated in Chronic Lymphocytic Leukemia Hematopoietic Stem Cells.PDF

Download (113.34 kB)
dataset
posted on 20.04.2018, 04:05 by 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, Antonio Francesco Campese, Paolo Di Bartolomeo, Isabella Screpanti, Emanuela Rosati, Franca Falzetti, Paolo Sportoletti

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.

History

Licence

Exports