caa a22 4500 60617561X CHVBK 20210128100743.0 cr unu---uuuuu 210128e20150601xx s 000 0 eng 10.1007/s00018-015-1867-5 doi (NATIONALLICENCE)springer-10.1007/s00018-015-1867-5 Targeting PI3K/AKT/mTOR network for treatment of leukemia [Elektronische Daten] [Jessika Bertacchini, Nazanin Heidari, Laura Mediani, Silvano Capitani, Mohammad Shahjahani, Ahmad Ahmadzadeh, Najmaldin Saki] Objective: Increased activity of PI3K/AKT/mTOR pathway has been observed in a huge number of malignancies. This pathway can function as a prosurvival factor in leukemia stem cells and early committed leukemic precursors and its inhibition is regarded as a therapeutic approach. Accordingly, the aim of this review is to evaluate the PI3K/Akt/mTOR inhibitors used in leukemia models. Discussion: Inhibition of the PI3K/AKT/mTOR pathway has been reported to have beneficial therapeutic effects in leukemias, both in vitro in leukemia cell lines and in vivo in animal models. Overall, the use of dual PI3K/mTOR inhibitor, dual Akt/RTK inhibitor, Akt inhibitor, selective inhibitor of PI3K, mTOR inhibitor and dual PI3K/PDK1 inhibitor in CML, AML, APL, CLL, B-ALL and T-ALL has a better therapeutic effect than conventional treatments. Conclusions: Targeting the PI3K/Akt/mTOR pathway may have pro-apoptotic and antiproliferative effects on hematological malignancies. Furthermore, modulation of miRNA can be used as a novel therapeutic approach to regulate the PI3K/Akt/mTOR pathway. However, both aspects require further clinical studies. Springer Basel, 2015 PI3K nationallicence Akt nationallicence mTOR nationallicence Rapamycin nationallicence Leukemia nationallicence MicroRNAs nationallicence Kinase inhibitors nationallicence Bertacchini Jessika Department of Surgery, Medicine, Dentistry and Morphology, University of Modena and Reggio Emilia, Modena, Italy aut Heidari Nazanin Health Research Institute, Research Center of Thalassemia and Hemoglobinopathy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran aut Mediani Laura Department of Surgery, Medicine, Dentistry and Morphology, University of Modena and Reggio Emilia, Modena, Italy aut Capitani Silvano Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara, Italy aut Shahjahani Mohammad Health Research Institute, Research Center of Thalassemia and Hemoglobinopathy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran aut Ahmadzadeh Ahmad Health Research Institute, Research Center of Thalassemia and Hemoglobinopathy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran aut Saki Najmaldin Health Research Institute, Research Center of Thalassemia and Hemoglobinopathy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran aut Cellular and Molecular Life Sciences Springer Basel 72/12(2015-06-01), 2337-2347 1420-682X 72:12<2337 2015 72 18 https://doi.org/10.1007/s00018-015-1867-5 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 review-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00018-015-1867-5 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Bertacchini Jessika Department of Surgery, Medicine, Dentistry and Morphology, University of Modena and Reggio Emilia, Modena, Italy aut NATIONALLICENCE 700 1- Heidari Nazanin Health Research Institute, Research Center of Thalassemia and Hemoglobinopathy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran aut NATIONALLICENCE 700 1- Mediani Laura Department of Surgery, Medicine, Dentistry and Morphology, University of Modena and Reggio Emilia, Modena, Italy aut NATIONALLICENCE 700 1- Capitani Silvano Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara, Italy aut NATIONALLICENCE 700 1- Shahjahani Mohammad Health Research Institute, Research Center of Thalassemia and Hemoglobinopathy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran aut NATIONALLICENCE 700 1- Ahmadzadeh Ahmad Health Research Institute, Research Center of Thalassemia and Hemoglobinopathy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran aut NATIONALLICENCE 700 1- Saki Najmaldin Health Research Institute, Research Center of Thalassemia and Hemoglobinopathy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran aut NATIONALLICENCE 773 0- Cellular and Molecular Life Sciences Springer Basel 72/12(2015-06-01), 2337-2347 1420-682X 72:12<2337 2015 72 18