TY - JOUR
T1 - Interleukin-23 acts as antitumor agent on childhood B-acute lymphoblastic leukemia cells
AU - Cocco, Claudia
AU - Canale, Sara
AU - Frasson, Chiara
AU - Di Carlo, Emma
AU - Ognio, Emanuela
AU - Ribatti, Domenico
AU - Prigione, Ignazia
AU - Basso, Giuseppe
AU - Airoldi, Irma
PY - 2010/11/11
Y1 - 2010/11/11
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=78149428394&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=78149428394&partnerID=8YFLogxK
U2 - 10.1182/blood-2009-10-248245
DO - 10.1182/blood-2009-10-248245
M3 - Article
C2 - 20671120
AN - SCOPUS:78149428394
VL - 116
SP - 3887
EP - 3898
JO - Blood
JF - Blood
SN - 0006-4971
IS - 19
ER -