Open AccessInterleukin-27 inhibits pediatric B-acute lymphoblastic leukemia cell spreading in a preclinical model
Author(s) -
S Canale,
Claudia Cocco,
Chiara Frasson,
Elena Seganfreddo,
Emma Di Carlo,
Emanuela Ognio,
Carlo Sorrentino,
Doménico Ribatti,
Alessia Zorzoli,
Giuseppe Basso,
Carlo Dufour,
Irma Airoldi
Publication year - 2011
Publication title -
leukemia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.539
H-Index - 192
eISSN - 1476-5551
pISSN - 0887-6924
DOI - 10.1038/leu.2011.158
Subject(s) - bone marrow , medicine , cytokine , immunology , leukemia , in vivo , b cell , cancer research , angiogenesis , spleen , biology , antibody , microbiology and biotechnology
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.