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.
NOTCH1 is aberrantly activated in chronic lymphocytic leukemia hematopoietic stem cells / Di Ianni, M., Baldoni, S., Del Papa, B., Aureli, P., Dorillo, E., De Falco, F., Albi, E., Varasano, E., Di Tommaso, A., Giancola, R., Accorsi, P., Rotta, G., Rompietti, C., Barcelos, E.C.S., Campese, A.F., Di Bartolomeo, P., Screpanti, I., Rosati, E., Falzetti, F., Sportoletti, P.. - In: FRONTIERS IN ONCOLOGY. - ISSN 2234-943X. - ELETTRONICO. - 8:APR(2018), pp. 1-7. [10.3389/fonc.2018.00105]
NOTCH1 is aberrantly activated in chronic lymphocytic leukemia hematopoietic stem cells
Campese, Antonio Francesco;Screpanti, Isabella;
2018
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.| File | Dimensione | Formato | |
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