Publications

Authors:

Takam Kamga, Paul; Dal Collo, Giada; Midolo, Martina; Adamo, Annalisa; Delfino, Pietro; Mercuri, Angela; Cesaro, Simone; Mimiola, Elda; Bonifacio, Massimiliano; Andreini, Angelo; Chilosi, Marco; Krampera, Mauro

Title:

Inhibition of Notch signaling enhances chemosensitivity in B cell precursor acute lymphoblastic leukemia

Year:

2019

Type of item:

Articolo in Rivista

Tipologia ANVUR:

Articolo su rivista

Language:

Inglese

Format:

Elettronico

Referee:

No

Name of journal:

Cancer Research

ISSN of journal:

0008-5472

N° Volume:

79

Number or Folder:

3

Page numbers:

639-649

Keyword:

Notch signaling, B -ALL, chemotherapy

Short description of contents:

Notch3 and Notch4 support survival of primary B cell acute lymphoblastic leukemia (B-ALL) cells, suggesting a role for Notch signaling in drug response. Here we used in vitro, in silico, and in vivo mouse xenograft model-based approaches to define the role of the Notch pathway in B-ALL chemosensitivity. We observed significant Notch receptor and ligand expression in B-ALL primary cells and cell lines. Primary leukemia cells from high-risk patients overexpressed Notch3, Notch4, and Jagged2 while displaying a reduction in expression levels of Notch1-4 following chemotherapy. We then analyzed in vitro, cell survival of B-ALL cells treated with conventional chemotherapeutic agents alone or in combination with Notch signaling inhibitors. Gamma-secretase inhibitors (GSI) and anti-Notch4 were all capable of potentiating drug-induced cell death in B-ALL cells by upregulating intracellular levels of reactive oxygen species, which in turn modulated mTOR, NF-κB, and ERK expression. In NOG-mouse-based xenograft models of B-ALL, co-administration of the Notch inhibitor GSI-XII with the chemotherapeutic agent Ara-C lowered bone marrow leukemic burden compared to DMSO or Ara-C alone, thus prolonging mouse survival. Overall, our results support the potential effectiveness of Notch inhibitors in B-ALL patients.

Note:

pii: canres.1617.2018

Product ID:

105915

Handle IRIS:

11562/989675

Last Modified:

November 15, 2022

Bibliographic citation:

Takam Kamga, Paul; Dal Collo, Giada; Midolo, Martina; Adamo, Annalisa; Delfino, Pietro; Mercuri, Angela; Cesaro, Simone; Mimiola, Elda; Bonifacio, Massimiliano; Andreini, Angelo; Chilosi, Marco; Krampera, Mauro, Inhibition of Notch signaling enhances chemosensitivity in B cell precursor acute lymphoblastic leukemia «Cancer Research» , vol. 79 , n. 3 , 2019 , pp. 639-649

Consulta la scheda completa presente nel repository istituzionale della Ricerca di Ateneo