title: Notch-3 and Notch-4 signaling rescue from apoptosis human B-ALL cells in contact with human bone marrow-derived mesenchymal stromal cells.
abstract: Although many literature data are available on the role of Notch signaling in T-cell acute lymphoblastic leukemia (ALL) biology, the importance of this molecular pathway in the development of B-lineage ALL (B-ALL) cells in the BM microenvironment is unknown so far. In this study, we used anti-Notch molecules neutralizing Abs and γ-secretase inhibitor (GSI) XII to investigate the role of the Notch signaling pathway in the promotion of human B-ALL cell survival in presence of stromal cell support. The treatment with combinations of anti-Notch molecule neutralizing Abs resulted in the decrease of B-ALL cell survival, either cultured alone or cocultured in presence of stromal cells from normal donors and B-ALL patients. Interestingly, the inhibition of Notch-3 and -4 or Jagged-1/-2 and DLL-1 resulted in a dramatic increase of apoptotic B-ALL cells by 3 days, similar to what is obtained by blocking all Notch signaling with the GSI XII. Our data suggest that the stromal cell-mediated antiapoptotic effect on B- ALL cells is mediated by Notch-3 and -4 or Jagged-1/-2 and DLL-1 in a synergistic manner.
authors: Stem Cell Research Laboratory, Section of Hematology, Department of Medicine, University of Verona, Verona, Italy.
authors: Armel Hervé
authors: AH
authors: Nwabo Kamdje
authors: Federico
authors: F
authors: Mosna
authors: Francesco
authors: F
authors: Bifari
authors: Veronica
authors: V
authors: Lisi
authors: Giulio
authors: G
authors: Bassi
authors: Giorgio
authors: G
authors: Malpeli
authors: Mario
authors: M
authors: Ricciardi
authors: Omar
authors: O
authors: Perbellini
authors: Maria Teresa
authors: MT
authors: Scupoli
authors: Giovanni
authors: G
authors: Pizzolo
authors: Mauro
authors: M
authors: Krampera