Details

Autor(en) / Beteiligte

• Nwabo Kamdje, Armel Hervé
• Mosna, Federico
• Bifari, Francesco
• Lisi, Veronica
• Bassi, Giulio
• Malpeli, Giorgio
• Ricciardi, Mario
• Perbellini, Omar
• Scupoli, Maria Teresa
• Pizzolo, Giovanni
• Krampera, Mauro

Titel

Notch-3 and Notch-4 signaling rescue from apoptosis human B-ALL cells in contact with human bone marrow–derived mesenchymal stromal cells

Ist Teil von

• Blood, 2011-07, Vol.118 (2), p.380-389

Ort / Verlag

Washington, DC: Elsevier Inc

Erscheinungsjahr

2011

Quelle

Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals

Beschreibungen/Notizen

• 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.