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

Canale, S; Cocco, C; Frasson, C; Seganfreddo, E; Di Carlo, E; Ognio, E; Sorrentino, C; Ribatti, D; Zorzoli, A; Basso, G; Dufour, C; Airoldi, I

Canale, S; Cocco, C; Frasson, C; Seganfreddo, E; Di Carlo, E; Ognio, E; Sorrentino, C; Ribatti, D; Zorzoli, A; Basso, G; Dufour, C; Airoldi, I.

Afiliación

Canale S; AIRC Laboratory of Immunology and Tumors, Department of Experimental and Laboratory Medicine, G. Gaslini Institute, Genova, Italy.

Leukemia ; 25(12): 1815-24, 2011 Dec.

Article en En | MEDLINE | ID: mdl-21701492

RESUMEN

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.

Asunto(s)

Apoptosis; Interleucina-17/uso terapéutico; Leucemia de Células B/patología; Leucemia de Células B/prevención & control; Leucemia-Linfoma Linfoblástico de Células Precursoras/patología; Leucemia-Linfoma Linfoblástico de Células Precursoras/prevención & control; Adolescente; Animales; Biomarcadores de Tumor/genética; Biomarcadores de Tumor/metabolismo; Western Blotting; Proliferación Celular; Pollos; Niño; Preescolar; Membrana Corioalantoides/efectos de los fármacos; Membrana Corioalantoides/metabolismo; Membrana Corioalantoides/patología; Femenino; Citometría de Flujo; Perfilación de la Expresión Génica; Humanos; Técnicas para Inmunoenzimas; Lactante; Leucemia de Células B/metabolismo; Masculino; Ratones; Ratones Endogámicos NOD; Ratones SCID; Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo; ARN Mensajero/genética; Reacción en Cadena en Tiempo Real de la Polimerasa; Reacción en Cadena de la Polimerasa de Transcriptasa Inversa; Células Tumorales Cultivadas

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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Leucemia de Células B / Apoptosis / Interleucina-17 / Leucemia-Linfoma Linfoblástico de Células Precursoras Tipo de estudio: Guideline Límite: Adolescent / Animals / Child / Child, preschool / Female / Humans / Infant / Male Idioma: En Revista: Leukemia Asunto de la revista: HEMATOLOGIA / NEOPLASIAS Año: 2011 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Reino Unido

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