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

作者：Kamdje Armel Herve Nwabo; Mosna Federico; Bifari Francesco; Lisi Veronica; Bassi Giulio; Malpeli Giorgio; Ricciardi Mario; Perbellini Omar; Scupoli Maria Teresa; Pizzolo Giovanni; Krampera Mauro^*

来源：Blood, 2011, 118(2): 380-389.

DOI：10.1182/blood-2010-12-326694

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 gamma-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. (Blood.2011;118(2):380-389)

• 出版日期2011-7-14