Cytotoxic activity of the novel Akt inhibitor, MK-2206, in T-cell acute lymphoblastic leukemia. (Articolo in rivista)

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  • Cytotoxic activity of the novel Akt inhibitor, MK-2206, in T-cell acute lymphoblastic leukemia. (Articolo in rivista) (literal)
Anno
  • 2012-01-01T00:00:00+01:00 (literal)
Alternative label
  • Simioni C, Neri LM, Tabellini G, Ricci F, Bressanin D, Chiarini F, Evangelisti C, Cani A, Tazzari PL, Melchionda F, Pagliaro P, Pession A, McCubrey JA, Capitani S, Martelli AM. (2012)
    Cytotoxic activity of the novel Akt inhibitor, MK-2206, in T-cell acute lymphoblastic leukemia.
    in Leukemia
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Simioni C, Neri LM, Tabellini G, Ricci F, Bressanin D, Chiarini F, Evangelisti C, Cani A, Tazzari PL, Melchionda F, Pagliaro P, Pession A, McCubrey JA, Capitani S, Martelli AM. (literal)
Pagina inizio
  • 2336 (literal)
Pagina fine
  • 2342 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume
  • 26 (literal)
Rivista
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroFascicolo
  • 11 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
  • Department of Morphology and Embryology, University of Ferrara, Ferrara, Italy; Department of Biomedical Sciences and Biotechnology, University of Brescia, Brescia, Italy; Immunohaematology and Transfusion Center, Policlinico S.Orsola-Malpighi, Bologna, Italy; Department of Human Anatomy, University of Bologna, Bologna, Italy; Institute of Molecular Genetics, National Research Council-Rizzoli Orthopedic Institute, Bologna, Italy; Paediatric Oncology and Hematology Unit Lalla Seràgnoli, University of Bologna, Bologna, Italy; Department of Microbiology and Immunology, School of Medicine, East Carolina University, Greenville, NC, USA (literal)
Titolo
  • Cytotoxic activity of the novel Akt inhibitor, MK-2206, in T-cell acute lymphoblastic leukemia. (literal)
Abstract
  • T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive neoplastic disorder arising from T-cell progenitors. T-ALL accounts for 15% of newly diagnosed ALL cases in children and 25% in adults. Although the prognosis of T-ALL has improved, due to the use of polychemotherapy schemes, the outcome of relapsed/chemoresistant T-ALL cases is still poor. A signaling pathway that is frequently upregulated in T-ALL, is the phosphatidylinositol 3-kinase/Akt/mTOR network. To explore whether Akt could represent a target for therapeutic intervention in T-ALL, we evaluated the effects of the novel allosteric Akt inhibitor, MK-2206, on a panel of human T-ALL cell lines and primary cells from T-ALL patients. MK-2206 decreased T-ALL cell line viability by blocking leukemic cells in the G(0)/G(1) phase of the cell cycle and inducing apoptosis. MK-2206 also induced autophagy, as demonstrated by an increase in the 14-kDa form of LC3A/B. Western blotting analysis documented a concentration-dependent dephosphorylation of Akt and its downstream targets, GSK-3?/? and FOXO3A, in response to MK-2206. MK-2206 was cytotoxic to primary T-ALL cells and induced apoptosis in a T-ALL patient cell subset (CD34(+)/CD4(-)/CD7(-)), which is enriched in leukemia-initiating cells. Taken together, our findings indicate that Akt inhibition may represent a potential therapeutic strategy in T-ALL. (literal)
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