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Acute Leukemias

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

Leukemia volume 25, pages 1815–1824 (2011)Cite this article

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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.

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Acknowledgements

This work was supported by grants from Associazione Italiana Ricerca sul Cancro (AIRC) Milano, Italy (Grant No. 4014 to IA), from Italian Ministry of Health (RF, RC, 5/1000, Progetto Strategico Oncologico 2006 rif070701).

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Authors and Affiliations

  1. Department of Experimental and Laboratory Medicine, A.I.R.C. Laboratory of Immunology and Tumors, G. Gaslini Institute, Genova, Italy

    S Canale, C Cocco, A Zorzoli & I Airoldi

  2. Department of Pediatrics, Division of Hematology Oncology, University of Padova, Padova, Italy

    C Frasson, E Seganfreddo & G Basso

  3. Department of Oncology and Neurosciences, ‘G. d’Annunzio’ University and Ce.S.I. Aging Research Center, ‘G. d’Annunzio’ University Foundation, Chieti, Italy

    E Di Carlo & C Sorrentino

  4. National Institute for Cancer Research, Animal Model Facility, Genova, Italy

    E Ognio

  5. Department of Human Anatomy and Histology, University of Bari, Bari, Italy

    D Ribatti

  6. Department of Oncology/Hematology, Hematology Unit, G. Gaslini Institute, Genova, Italy

    C Dufour

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  1. S Canale
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  2. C Cocco
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Correspondence to I Airoldi.

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Canale, S., Cocco, C., Frasson, C. et al. Interleukin-27 inhibits pediatric B-acute lymphoblastic leukemia cell spreading in a preclinical model. Leukemia 25, 1815–1824 (2011). https://doi.org/10.1038/leu.2011.158

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