Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
, 118 (2), 380-9

Notch-3 and Notch-4 Signaling Rescue From Apoptosis Human B-ALL Cells in Contact With Human Bone Marrow-Derived Mesenchymal Stromal Cells

Affiliations

Notch-3 and Notch-4 Signaling Rescue From Apoptosis Human B-ALL Cells in Contact With Human Bone Marrow-Derived Mesenchymal Stromal Cells

Armel Hervé Nwabo Kamdje et al. Blood.

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.

Similar articles

See all similar articles

Cited by 39 articles

See all "Cited by" articles

Publication types

MeSH terms

LinkOut - more resources

Feedback