Interleukin-27 inhibits the growth of pediatric acute myeloid leukemia in NOD/SCID/Il2rg -/- mice

Alessia Zorzoli, Emma Di Carlo, Claudia Cocco, Emanuela Ognio, Domenico Ribatti, Elisa Ferretti, Carlo Dufour, Franco Locatelli, Daniela Montagna, Irma Airoldi

Research output: Contribution to journalArticle

Abstract

Purpose: Acute myeloid leukemia (AML) accounts for more than half of fatal cases in all pediatric leukemia patients; this observation highlights the need of more effective therapies. Thus, we investigated whether interleukin (IL)-27, an immunomodulatory cytokine, functions as an antitumor agent against pediatric AML cells. Experimental Design: Expression of WSX-1 and gp130 on AML cells from 16 pediatric patients was studied by flow cytometry. Modulation of leukemia cell proliferation or apoptosis upon IL-27 treatment in vitro was tested by bromodeoxyuridine/propidium iodide (PI) and Ki67, or Annexin V/PI staining and flow cytometric analysis. The angiogenic potential of AML cells treated or not with IL-27 was studied by chorioallantoic membrane assay and PCR array. In vivo studies were carried out using nonobese diabetic/ severe combined immunodeficient (NOD/SCID)/Il2rg -/- mice injected intravenously with five pediatric AML cell samples. Leukemic cells engrafted in PBS and IL-27-treated animals were studied by immuno-histochemical/morphologic analysis and by PCR array for expression angiogenic/dissemination-related genes. Results: We provided the first demonstration that (i) AML cells injected into NOD/SCID/Il2rg -/- mice gave rise to leukemia dissemination that was severely hampered by IL-27, (ii) compared with controls, leukemia cells harvested from IL-27-treated mice showed significant reduction of their angiogenic and spreading related genes, and (iii) similarly to what was observed in vivo, IL-27 reduced in vitro AML cell proliferation and modulated the expression of different genes involved in the angiogenic/spreading process. Conclusion: These results provide an experimental rationale for the development of future clinical trials aimed at evaluating the toxicity and efficacy of IL-27.

Original languageEnglish
Pages (from-to)1630-1640
Number of pages11
JournalClinical Cancer Research
Volume18
Issue number6
DOIs
Publication statusPublished - Mar 15 2012

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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