Multiple myeloma (MM) is a diffuse hematologic tumor that is still incurable, despite the development of innovative therapies. One of the most relevant obstacles to currently available treatments is the protection from drug-induced apoptosis caused by the crosstalk of MM cells and bone marrow stromal cells (BMSCs), which provides a source of pro-survival and growth factors that promotes drug resistance, that causes patients' relapse and contribute to MM fatal outcome. The overexpression of the two Notch ligands Jag1 and Jag2 by tumor cells causes the hyperactivation of the Notch signaling both in the neighboring MM cells and in the cells of the tumor microenvironment. To test if Jag1/2 double-silencing (Jag1/2KD) in MM cells prevented BMSC-mediated drug resistance, we established a co-culture system composed of human myeloma cell lines (HMCLs) and the human BMSC line HS5, and compared the efficacy of commonly-used drugs, i.e. bortezomib, melphalan and lenalidomide between control and Jag1/2KD co-cultures.

Notch signaling promotes bone marrow-induced drug resistance in multiple myeloma through the regulation of the CXCR4/CXCL12 system / M. Colombo, M. Mazzola, M. Barbieri, N. Platonova, M.T. Palano, S. Garavelli, D. Giannandrea, E. Lazzari, A. Basile, A.S. Pistocchi, A. Neri, R. Chiaramonte. ((Intervento presentato al 60. convegno Annual Meeting of the Italian Cancer society tenutosi a Milano nel 2018.

Notch signaling promotes bone marrow-induced drug resistance in multiple myeloma through the regulation of the CXCR4/CXCL12 system

M. Colombo
;
M. Mazzola;M. Barbieri;N. Platonova;M.T. Palano;S. Garavelli;E. Lazzari;A. Basile;A.S. Pistocchi;A. Neri;R. Chiaramonte
2018

Abstract

Multiple myeloma (MM) is a diffuse hematologic tumor that is still incurable, despite the development of innovative therapies. One of the most relevant obstacles to currently available treatments is the protection from drug-induced apoptosis caused by the crosstalk of MM cells and bone marrow stromal cells (BMSCs), which provides a source of pro-survival and growth factors that promotes drug resistance, that causes patients' relapse and contribute to MM fatal outcome. The overexpression of the two Notch ligands Jag1 and Jag2 by tumor cells causes the hyperactivation of the Notch signaling both in the neighboring MM cells and in the cells of the tumor microenvironment. To test if Jag1/2 double-silencing (Jag1/2KD) in MM cells prevented BMSC-mediated drug resistance, we established a co-culture system composed of human myeloma cell lines (HMCLs) and the human BMSC line HS5, and compared the efficacy of commonly-used drugs, i.e. bortezomib, melphalan and lenalidomide between control and Jag1/2KD co-cultures.
20-set-2018
Settore MED/04 - Patologia Generale
Settore BIO/13 - Biologia Applicata
Settore BIO/11 - Biologia Molecolare
Notch signaling promotes bone marrow-induced drug resistance in multiple myeloma through the regulation of the CXCR4/CXCL12 system / M. Colombo, M. Mazzola, M. Barbieri, N. Platonova, M.T. Palano, S. Garavelli, D. Giannandrea, E. Lazzari, A. Basile, A.S. Pistocchi, A. Neri, R. Chiaramonte. ((Intervento presentato al 60. convegno Annual Meeting of the Italian Cancer society tenutosi a Milano nel 2018.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/589000
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