title: Interleukin-27 inhibits pediatric B-acute lymphoblastic leukemia cell spreading in a preclinical model.
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.
authors.affiliation: AIRC Laboratory of Immunology and Tumors, Department of Experimental and Laboratory Medicine, G. Gaslini Institute, Genova, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Canale
authors.forename: C
authors.initials: C
authors.lastname: Cocco
authors.forename: C
authors.initials: C
authors.lastname: Frasson
authors.forename: E
authors.initials: E
authors.lastname: Seganfreddo
authors.forename: E
authors.initials: E
authors.lastname: Di Carlo
authors.forename: E
authors.initials: E
authors.lastname: Ognio
authors.forename: C
authors.initials: C
authors.lastname: Sorrentino
authors.forename: D
authors.initials: D
authors.lastname: Ribatti
authors.forename: A
authors.initials: A
authors.lastname: Zorzoli
authors.forename: G
authors.initials: G
authors.lastname: Basso
authors.forename: C
authors.initials: C
authors.lastname: Dufour
authors.forename: I
authors.initials: I
authors.lastname: Airoldi
mesh_terms: D000293:Adolescent; D000818:Animals; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D049109:Cell Proliferation; D002645:Chickens; D002648:Child; D002675:Child, Preschool; D049033:Chorioallantoic Membrane / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D006801:Humans; D007124:Immunoenzyme Techniques; D007223:Infant; D020381:Interleukin-17 / Q000627:therapeutic use*; D015448:Leukemia, B-Cell / Q000378:metabolism / Q000473:pathology* / Q000517:prevention & control*; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000378:metabolism / Q000473:pathology* / Q000517:prevention & control*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor; D020381:Interleukin-17; D012333:RNA, Messenger