Interleukin-23 acts as antitumor agent on childhood B-acute lymphoblastic leukemia cells

Claudia Cocco, Sara Canale, Chiara Frasson, Emma Di Carlo, Emanuela Ognio, Domenico Ribatti, Ignazia Prigione, Giuseppe Basso, Irma Airoldi

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)3887-3898
Number of pages12
JournalBlood
Volume116
Issue number19
DOIs
Publication statusPublished - Nov 11 2010

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

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