Interleukin-27 inhibits pediatric B-acute lymphoblastic leukemia cell spreading in a preclinical model

S. Canale, C. Cocco, C. Frasson, E. Seganfreddo, E. Di Carlo, E. Ognio, C. Sorrentino, D. Ribatti, A. Zorzoli, G. Basso, C. Dufour, I. Airoldi

Research output: Contribution to journalArticle

Abstract

B-acute lymphoblastic leukemia (B-ALL) represents the most common pediatric hematological tumor that derives from the aberrant proliferation of early B lymphocytes in the bone marrow. Although most of the B-ALL children take advantage from current therapeutic protocols, some patients relapse and need alternative therapies. With this background, we investigated whether interleukin (IL)-27, an immunomodulatory cytokine with antitumor properties, may function as an antitumor agent against pediatric B-ALL cells. Here we show for the first time that pediatric B-ALL cells functional IL-27R and that IL-27 dampens directly tumor growth in vivo and in vitro through mechanisms elucidated in this study. The novelty of these results deals with the first demonstration that (1) B-ALL cells from pediatric patients injected intravenously (i.v.) into NOD/SCID/Il2rg/(NSG) mice gave rise to leukemic spreading that was severely hampered by IL-27; (2) IL-27-treated mice, compared with controls, showed significant reduction of putative B-ALL-initiating cells and blasts in the peripheral blood (PB), bone marrow (BM) and spleen; and that (3) IL-27 reduced in vitro B-ALL cell proliferation and angiogenesis, induced apoptosis and downregulated miR-155. Our results strongly encourage the development of future clinical trials to evaluate the toxicity and efficacy of IL-27 in childhood B-ALL patients.

Original languageEnglish
Pages (from-to)1815-1824
Number of pages10
JournalLeukemia
Volume25
Issue number12
DOIs
Publication statusPublished - Dec 2011

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Keywords

  • cytokine receptors
  • cytokines
  • pediatric acute leukemia

ASJC Scopus subject areas

  • Hematology
  • Cancer Research
  • Anesthesiology and Pain Medicine

Cite this

Canale, S., Cocco, C., Frasson, C., Seganfreddo, E., Di Carlo, E., Ognio, E., Sorrentino, C., Ribatti, D., Zorzoli, A., Basso, G., Dufour, C., & Airoldi, I. (2011). Interleukin-27 inhibits pediatric B-acute lymphoblastic leukemia cell spreading in a preclinical model. Leukemia, 25(12), 1815-1824. https://doi.org/10.1038/leu.2011.158