학술논문
NOTCH1 Is Aberrantly Activated in Chronic Lymphocytic Leukemia Hematopoietic Stem Cells
Document Type
article
Author
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
Source
Frontiers in Oncology, Vol 8 (2018)
Subject
Language
English
ISSN
2234-943X
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.