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

Leukemia. 2011 Dec;25(12):1815-24. doi: 10.1038/leu.2011.158. Epub 2011 Jun 24.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Animals
  • Apoptosis*
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Blotting, Western
  • Cell Proliferation
  • Chickens
  • Child
  • Child, Preschool
  • Chorioallantoic Membrane / drug effects
  • Chorioallantoic Membrane / metabolism
  • Chorioallantoic Membrane / pathology
  • Female
  • Flow Cytometry
  • Gene Expression Profiling
  • Humans
  • Immunoenzyme Techniques
  • Infant
  • Interleukin-17 / therapeutic use*
  • Leukemia, B-Cell / metabolism
  • Leukemia, B-Cell / pathology*
  • Leukemia, B-Cell / prevention & control*
  • Male
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / metabolism
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / pathology*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / prevention & control*
  • RNA, Messenger / genetics
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tumor Cells, Cultured


  • Biomarkers, Tumor
  • Interleukin-17
  • RNA, Messenger