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

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Interleukin-27
SCID Mice
Acute Myeloid Leukemia
Myeloid Cells
Pediatrics
Growth
Leukemia
Propidium
Cell Proliferation
Chorioallantoic Membrane
Polymerase Chain Reaction
Annexin A5
Bromodeoxyuridine
Antineoplastic Agents
Genes
Flow Cytometry
Research Design
Clinical Trials
Apoptosis
Staining and Labeling

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Interleukin-27 inhibits the growth of pediatric acute myeloid leukemia in NOD/SCID/Il2rg -/- mice. / Zorzoli, Alessia; Di Carlo, Emma; Cocco, Claudia; Ognio, Emanuela; Ribatti, Domenico; Ferretti, Elisa; Dufour, Carlo; Locatelli, Franco; Montagna, Daniela; Airoldi, Irma.

In: Clinical Cancer Research, Vol. 18, No. 6, 15.03.2012, p. 1630-1640.

Research output: Contribution to journalArticle

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AU - Di Carlo, Emma

AU - Cocco, Claudia

AU - Ognio, Emanuela

AU - Ribatti, Domenico

AU - Ferretti, Elisa

AU - Dufour, Carlo

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