Involvement of Notch-1 Signaling in Bone Marrow Stroma-mediated De Novo Drug Resistance of Myeloma and Other Malignant Lymphoid Cell Lines
Document Type
Article
Publication Date
2004
Digital Object Identifier (DOI)
https://doi.org/10.1182/blood-2003-07-2340
Abstract
The bone marrow (BM) microenvironment plays a critical role in malignant cell growth, patient survival, and response to chemotherapy in hematologic malignancies. However, mechanisms associated with this environmental influence remain unclear. In this study, we investigated the role of Notch family proteins in myeloma and other malignant lymphoid cell line growth and response to chemotherapeutic drugs. All 8 tested cell lines expressed Notch-3 and Notch-4; 7 cell lines expressed Notch-1; and 6 expressed Notch-2 proteins. Interaction with BM stroma (BMS) activated Notch signaling in tumor cells. However, activation of only Notch-1, but not Notch-2, resulted in protection of tumor cells from melphalan- and mitoxantrone-induced apoptosis. This protection was associated with up-regulation of p21WAF/Cip and growth inhibition of cells. Overexpression of Notch-1 in Notch-1- U266 myeloma cells up-regulated p21 and resulted in protection from drug-induced apoptosis. Thus, this is a first report demonstrating that Notch-1 signaling may be a primary mechanism mediating the BMS influence on hematologic malignant cell growth and survival. (Blood. 2004; 103:3503-3510)
Was this content written or created while at USF?
Yes
Citation / Publisher Attribution
Blood, v. 103, issue 9, p. 3503-3510
Scholar Commons Citation
Nefedova, Yulia; Cheng, Pingyan; Alsina, Melissa; Dalton, William S.; and Gabrilovich, Dmitry I., "Involvement of Notch-1 Signaling in Bone Marrow Stroma-mediated De Novo Drug Resistance of Myeloma and Other Malignant Lymphoid Cell Lines" (2004). Internal Medicine Faculty Publications. 191.
https://digitalcommons.usf.edu/intmed_facpub/191
