Dual PI3K/mTOR inhibition shows antileukemic activity in MLL-rearranged acute myeloid leukemia

In acute myeloid leukemia (AML), several signaling pathways such as the phosphatidylinositol-3-kinase/AKT and the mammalian target of rapamycin (PI3K/AKT/mTOR) pathway are deregulated and constitutively activated as a consequence of genetic and cytogenetic abnormalities. We tested the effectiveness...

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Veröffentlicht in:	Leukemia 2015-04, Vol.29 (4), p.828-838
Hauptverfasser:	Sandhöfer, N, Metzeler, K H, Rothenberg, M, Herold, T, Tiedt, S, Groiß, V, Carlet, M, Walter, G, Hinrichsen, T, Wachter, O, Grunert, M, Schneider, S, Subklewe, M, Dufour, A, Fröhling, S, Klein, H-G, Hiddemann, W, Jeremias, I, Spiekermann, K
Format:	Artikel
Sprache:	eng
Schlagworte:	1-Phosphatidylinositol 3-kinase 13/31 14/5 38/61 45/23 631/67/1990/283 631/67/1990/283/1897 631/80/86 96/95 Abnormalities Acute myeloid leukemia AKT protein Animals Anticancer properties Antineoplastic Agents - pharmacology Apoptosis Apoptosis - drug effects Cancer Research Cellular signal transduction Critical Care Medicine Cytogenetics Cytotoxicity Deregulation Drug Synergism Enzymes Extracellular signal-regulated kinase Gene Expression Regulation, Leukemic Gene Rearrangement Growth factors Health aspects Hematology Heterocyclic Compounds, 3-Ring - pharmacology Humans Imidazoles - pharmacology Inhibition Intensive Internal Medicine Kinases Leukemia Leukemia, Myeloid, Acute - drug therapy Leukemia, Myeloid, Acute - genetics Leukemia, Myeloid, Acute - metabolism Leukemia, Myeloid, Acute - pathology Medicine Medicine & Public Health Metabolic pathways Methods Mice Molecular targeted therapy Mutation Mutation rates Myeloid leukemia Myeloid-Lymphoid Leukemia Protein - genetics Myeloid-Lymphoid Leukemia Protein - metabolism Oncogene Proteins, Fusion - genetics Oncogene Proteins, Fusion - metabolism Oncology original-article Phosphatidylinositol 3-Kinases - antagonists & inhibitors Phosphatidylinositol 3-Kinases - genetics Phosphatidylinositol 3-Kinases - metabolism Phosphotransferases Proto-Oncogene Proteins c-akt - antagonists & inhibitors Proto-Oncogene Proteins c-akt - genetics Proto-Oncogene Proteins c-akt - metabolism Quinolines - pharmacology Rapamycin Regulation Sensitivity analysis Signal Transduction Signaling Sirolimus - pharmacology Subgroups Survival Analysis Synergistic effect TOR protein TOR Serine-Threonine Kinases - antagonists & inhibitors TOR Serine-Threonine Kinases - genetics TOR Serine-Threonine Kinases - metabolism Tumor Burden - drug effects Tumors Xenograft Model Antitumor Assays Xenografts Xenotransplantation
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