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 

TITLE=NOTCH1 Is Aberrantly Activated in Chronic Lymphocytic Leukemia Hematopoietic Stem Cells

JOURNAL=Frontiers in Oncology

VOLUME=8

YEAR=2018

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2018.00105

DOI=10.3389/fonc.2018.00105

ISSN=2234-943X

ABSTRACT=<p>To investigate chronic lymphocytic leukemia (CLL)-initiating cells, we assessed <italic>NOTCH1</italic> mutation/expression in hematopoietic stem cells (HSCs). In <italic>NOTCH1-</italic>mutated CLL, we detected subclonal mutations in 57% CD34+/CD38− HSCs. <italic>NOTCH1</italic> 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 <italic>NOTCH1</italic> 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.</p>