title: Interleukin-27 inhibits the growth of pediatric acute myeloid leukemia in NOD/SCID/Il2rg-/- mice.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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 immunohistochemical/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.
  
  
  CONCLUSIONS
  These results provide an experimental rationale for the development of future clinical trials aimed at evaluating the toxicity and efficacy of IL-27.
authors.affiliation: Department of Experimental and Laboratory Medicine, IRCCS G. Gaslini Institute, Genoa, Italy.
authors.forename: Alessia
authors.initials: A
authors.lastname: Zorzoli
authors.forename: Emma
authors.initials: E
authors.lastname: Di Carlo
authors.forename: Claudia
authors.initials: C
authors.lastname: Cocco
authors.forename: Emanuela
authors.initials: E
authors.lastname: Ognio
authors.forename: Domenico
authors.initials: D
authors.lastname: Ribatti
authors.forename: Elisa
authors.initials: E
authors.lastname: Ferretti
authors.forename: Carlo
authors.initials: C
authors.lastname: Dufour
authors.forename: Franco
authors.initials: F
authors.lastname: Locatelli
authors.forename: Daniela
authors.initials: D
authors.lastname: Montagna
authors.forename: Irma
authors.initials: I
authors.lastname: Airoldi
mesh_terms: D000293:Adolescent; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D049109:Cell Proliferation / Q000187:drug effects; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D020381:Interleukin-17 / Q000627:therapeutic use*; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009389:Neovascularization, Pathologic / Q000235:genetics; D023041:Xenograft Model Antitumor Assays; D055815:Young Adult
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D020381:Interleukin-17