期刊
BLOOD
卷 116, 期 19, 页码 3887-3898出版社
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2009-10-248245
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资金
- Associazione Italiana Ricerca sul Cancro, Milano, Italy [4014]
- Fondazione Cassa di Risparmio della Provincia di Chieti (CariChieti), Italy
- Fondazione Citta Della Speranza, Fondazione CARIPARO
- PRIN
- AIRC
Interleukin (IL)-23 is a proinflammatory cytokine belonging to the IL-12 superfamily. The antitumor activity of IL-23 is controversial, and it is unknown whether or not the cytokine can act directly on tumor cells. The aim of this study was to investigate the potential direct antitumor activity of IL-23 in pediatric B-acute lymphoblastic leukemia (B-ALL) cells and to unravel the molecular mechanisms involved. Here, we show, for the first time, that IL-23R is up-regulated in primary B-ALL cells, compared with normal early B lymphocytes, and that IL-23 dampens directly tumor growth in vitro and in vivo through the inhibition of tumor cell proliferation and induction of apoptosis. The latter finding is related to IL-23-induced upregulation of miR15a expression and the consequent down-regulation of BCL-2 protein expression in pediatric B-ALL cells. This study demonstrates that IL-23 possesses antileukemic activity and unravels the underlying mechanisms. Thus, IL-23 may be a candidate novel drug for the treatment of B-ALL patients unresponsive to current therapeutic standards. (Blood. 2010; 116(19):3887-3898)
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