{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T07:01:38Z","timestamp":1792047698338,"version":"4.4.0"},"reference-count":127,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2023,11,5]],"date-time":"2023-11-05T00:00:00Z","timestamp":1699142400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Medical University of Lodz, Poland","award":["503\/1-156-07\/503-11-001"],"award-info":[{"award-number":["503\/1-156-07\/503-11-001"]}]},{"name":"Medical University of Lodz, Poland","award":["2021\/43\/O\/NZ5\/02068"],"award-info":[{"award-number":["2021\/43\/O\/NZ5\/02068"]}]},{"name":"Polish National Science Centre (NCN)","award":["503\/1-156-07\/503-11-001"],"award-info":[{"award-number":["503\/1-156-07\/503-11-001"]}]},{"name":"Polish National Science Centre (NCN)","award":["2021\/43\/O\/NZ5\/02068"],"award-info":[{"award-number":["2021\/43\/O\/NZ5\/02068"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Blood malignancies remain a therapeutic challenge despite the development of numerous treatment strategies. The phosphatidylinositol-3 kinase (PI3K)\/protein kinase B\/mammalian target of rapamycin (PI3K\/Akt\/mTOR) signaling pathway plays a central role in regulating many cellular functions, including cell cycle, proliferation, quiescence, and longevity. Therefore, dysregulation of this pathway is a characteristic feature of carcinogenesis. Increased activation of PI3K\/Akt\/mTOR signaling enhances proliferation, growth, and resistance to chemo- and immunotherapy in cancer cells. Overactivation of the pathway has been found in various types of cancer, including acute and chronic leukemia. Inhibitors of the PI3K\/Akt\/mTOR pathway have been used in leukemia treatment since 2014, and some of them have improved treatment outcomes in clinical trials. Recently, new inhibitors of PI3K\/Akt\/mTOR signaling have been developed and tested both in preclinical and clinical models. In this review, we outline the role of the PI3K\/Akt\/mTOR signaling pathway in blood malignancies\u2019 cells and gather information on the inhibitors of this pathway that might provide a novel therapeutic opportunity against leukemia.<\/jats:p>","DOI":"10.3390\/cancers15215297","type":"journal-article","created":{"date-parts":[[2023,11,5]],"date-time":"2023-11-05T07:35:06Z","timestamp":1699169706000},"page":"5297","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":69,"title":["PI3K\/Akt\/mTOR Signaling Pathway in Blood Malignancies\u2014New Therapeutic Possibilities"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0796-9717","authenticated-orcid":false,"given":"Wojciech","family":"Wiese","sequence":"first","affiliation":[{"name":"Department of Clinical Chemistry and Biochemistry, Medical University of Lodz, Mazowiecka 5, 92-215 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4708-9164","authenticated-orcid":false,"given":"Julia","family":"Barczuk","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry and Biochemistry, Medical University of Lodz, Mazowiecka 5, 92-215 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga","family":"Racinska","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry and Biochemistry, Medical University of Lodz, Mazowiecka 5, 92-215 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0308-580X","authenticated-orcid":false,"given":"Natalia","family":"Siwecka","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry and Biochemistry, Medical University of Lodz, Mazowiecka 5, 92-215 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9206-1203","authenticated-orcid":false,"given":"Wioletta","family":"Rozpedek-Kaminska","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry and Biochemistry, Medical University of Lodz, Mazowiecka 5, 92-215 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Artur","family":"Slupianek","sequence":"additional","affiliation":[{"name":"Department of Pathology, Fox Chase Cancer Center, Temple University, Philadelphia, PA 19111, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Radoslaw","family":"Sierpinski","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Cardinal Stefan Wyszy\u0144ski University, 01-938 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ireneusz","family":"Majsterek","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry and Biochemistry, Medical University of Lodz, Mazowiecka 5, 92-215 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,11,5]]},"reference":[{"key":"ref_1","first-page":"79488","article-title":"Deaths: Leading Causes for 2017","volume":"68","author":"Heron","year":"2019","journal-title":"Natl. Vital Stat. Rep."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Karagianni, P., Giannouli, S., and Voulgarelis, M. (2021). From the (Epi)Genome to Metabolism and Vice Versa; Examples from Hematologic Malignancy. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22126321"},{"key":"ref_3","first-page":"1","article-title":"Epidemiology of Hematologic Malignancies in Real-World Settings: Findings From the Hemato-Oncology Latin America Observational Registry Study","volume":"5","author":"Chiattone","year":"2019","journal-title":"J. Glob. Oncol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.blre.2018.07.003","article-title":"Evolution of Survivorship in Lymphoma, Myeloma and Leukemia: Metamorphosis of the Field into Long Term Follow-up Care","volume":"33","author":"Damlaj","year":"2019","journal-title":"Blood Rev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3322\/caac.21590","article-title":"Cancer Statistics, 2020","volume":"70","author":"Siegel","year":"2020","journal-title":"CA Cancer J. Clin."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1038\/nrd2926","article-title":"Targeting the Phosphoinositide 3-Kinase Pathway in Cancer","volume":"8","author":"Liu","year":"2009","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Zou, Z., Tao, T., Li, H., and Zhu, X. (2020). MTOR Signaling Pathway and MTOR Inhibitors in Cancer: Progress and Challenges. Cell Biosci., 10.","DOI":"10.1186\/s13578-020-00396-1"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Nepstad, I., Hatfield, K.J., Gr\u00f8nnings\u00e6ter, I.S., and Reikvam, H. (2020). The PI3K-Akt-MTOR Signaling Pathway in Human Acute Myeloid Leukemia (AML) Cells. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21082907"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"113192","DOI":"10.1016\/j.yexcr.2022.113192","article-title":"Targeting PI3K\/AKT\/MTOR Pathway to Enhance the Anti-Leukemia Efficacy of Venetoclax","volume":"417","author":"Liu","year":"2022","journal-title":"Exp. Cell Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1745","DOI":"10.1002\/jcb.25559","article-title":"Targeting the MTOR Pathway in Leukemia","volume":"117","author":"Dinner","year":"2016","journal-title":"J. Cell Biochem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"101251","DOI":"10.1016\/j.beha.2021.101251","article-title":"Mechanisms for Resistance in AML Insights into Molecular Pathways Mediating Resistance to Venetoclax","volume":"34","author":"Konopleva","year":"2021","journal-title":"Best. Pract. Res. Clin. Haematol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"705627","DOI":"10.3389\/fonc.2021.705627","article-title":"Decoupling Lineage-Associated Genes in Acute Myeloid Leukemia Reveals Inflammatory and Metabolic Signatures Associated With Outcomes","volume":"11","author":"Abbas","year":"2021","journal-title":"Front. Oncol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Miricescu, D., Totan, A., Stanescu-Spinu, I.-I., Badoiu, S.C., Stefani, C., and Greabu, M. (2020). PI3K\/AKT\/MTOR Signaling Pathway in Breast Cancer: From Molecular Landscape to Clinical Aspects. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22010173"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1038\/nrc3860","article-title":"PI3K in Cancer: Divergent Roles of Isoforms, Modes of Activation and Therapeutic Targeting","volume":"15","author":"Thorpe","year":"2015","journal-title":"Nat. Rev. Cancer"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Tarantelli, C., Lupia, A., Stathis, A., and Bertoni, F. (2020). Is There a Role for Dual PI3K\/MTOR Inhibitors for Patients Affected with Lymphoma?. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21031060"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1038\/nri1056","article-title":"PI3K in Lymphocyte Development, Differentiation and Activation","volume":"3","author":"Okkenhaug","year":"2003","journal-title":"Nat. Rev. Immunol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1016\/j.immuni.2007.07.014","article-title":"P110\u03b3 and P110\u03b4 Phosphoinositide 3-Kinase Signaling Pathways Synergize to Control Development and Functions of Murine NK Cells","volume":"27","author":"Tassi","year":"2007","journal-title":"Immunity"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Kok, K., Nock, G.E., Verrall, E.A.G., Mitchell, M.P., Hommes, D.W., Peppelenbosch, M.P., and Vanhaesebroeck, B. (2009). Regulation of P110\u03b4 PI 3-Kinase Gene Expression. PLoS ONE, 4.","DOI":"10.1371\/journal.pone.0005145"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"7025","DOI":"10.1111\/febs.15692","article-title":"The Molecular Mechanisms Mediating Class II PI 3-kinase Function in Cell Physiology","volume":"288","author":"Koch","year":"2021","journal-title":"FEBS J."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.semcancer.2019.07.009","article-title":"PI3K\/Akt\/MTOR Inhibitors in Cancer: At the Bench and Bedside","volume":"59","author":"Alzahrani","year":"2019","journal-title":"Semin. Cancer Biol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"111690","DOI":"10.1016\/j.mrfmmm.2020.111690","article-title":"Targeting AKT\/PKB to Improve Treatment Outcomes for Solid Tumors","volume":"819\u2013820","author":"Iida","year":"2020","journal-title":"Mutat. Res. Fundam. Mol. Mech. Mutagen."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1158\/0008-5472.CAN-18-2738","article-title":"AKT as a Therapeutic Target for Cancer","volume":"79","author":"Song","year":"2019","journal-title":"Cancer Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1080\/13543784.2019.1676726","article-title":"Targeting AKT for Cancer Therapy","volume":"28","author":"Shariati","year":"2019","journal-title":"Expert Opin. Investig. Drugs"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Pinker, B., and Barciszewska, A.-M. (2022). MTOR Signaling and Potential Therapeutic Targeting in Meningioma. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23041978"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.jbior.2014.09.004","article-title":"Distinct Signaling Mechanisms of MTORC1 and MTORC2 in Glioblastoma Multiforme: A Tale of Two Complexes","volume":"57","author":"Gillick","year":"2015","journal-title":"Adv. Biol. Regul."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Barzegar Behrooz, A., Talaie, Z., Jusheghani, F., \u0141os, M.J., Klonisch, T., and Ghavami, S. (2022). Wnt and PI3K\/Akt\/MTOR Survival Pathways as Therapeutic Targets in Glioblastoma. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23031353"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"4587","DOI":"10.1007\/s11033-020-05435-1","article-title":"Role of PI3K\/AKT Pathway in Cancer: The Framework of Malignant Behavior","volume":"47","author":"Jiang","year":"2020","journal-title":"Mol. Biol. Rep."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1038\/s41419-020-02998-6","article-title":"PI3K\/AKT Pathway as a Key Link Modulates the Multidrug Resistance of Cancers","volume":"11","author":"Liu","year":"2020","journal-title":"Cell Death Dis."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"8045","DOI":"10.1007\/s11033-021-06739-6","article-title":"Small Molecules with Huge Impacts: The Role of MiRNA-Regulated PI3K Pathway in Human Malignancies","volume":"48","author":"Kashani","year":"2021","journal-title":"Mol. Biol. Rep."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1016\/j.ccell.2017.04.013","article-title":"A Pan-Cancer Proteogenomic Atlas of PI3K\/AKT\/MTOR Pathway Alterations","volume":"31","author":"Zhang","year":"2017","journal-title":"Cancer Cell"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"410","DOI":"10.21037\/atm-21-698","article-title":"PIK3CA Mutation Confers Resistance to Chemotherapy in Triple-Negative Breast Cancer by Inhibiting Apoptosis and Activating the PI3K\/AKT\/MTOR Signaling Pathway","volume":"9","author":"Hu","year":"2021","journal-title":"Ann. Transl. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1038\/s41568-019-0216-7","article-title":"The PI3K\u2013AKT Network at the Interface of Oncogenic Signalling and Cancer Metabolism","volume":"20","author":"Hoxhaj","year":"2020","journal-title":"Nat. Rev. Cancer"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2005","DOI":"10.1016\/j.celrep.2017.05.041","article-title":"Phosphorylation of TXNIP by AKT Mediates Acute Influx of Glucose in Response to Insulin","volume":"19","author":"Waldhart","year":"2017","journal-title":"Cell Rep."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"23798","DOI":"10.1074\/jbc.M113.482026","article-title":"Akt Phosphorylates HK-II at Thr-473 and Increases Mitochondrial HK-II Association to Protect Cardiomyocytes","volume":"288","author":"Roberts","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1042\/bj2450313","article-title":"Role of Fructose 2,6-Bisphosphate in the Control of Glycolysis in Mammalian Tissues","volume":"245","author":"Hue","year":"1987","journal-title":"Biochem. J."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"12526","DOI":"10.1073\/pnas.1302455110","article-title":"MTOR Complex 2-Akt Signaling at Mitochondria-Associated Endoplasmic Reticulum Membranes (MAM) Regulates Mitochondrial Physiology","volume":"110","author":"Betz","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Chiara, F., Castellaro, D., Marin, O., Petronilli, V., Brusilow, W.S., Juhaszova, M., Sollott, S.J., Forte, M., Bernardi, P., and Rasola, A. (2008). Hexokinase II Detachment from Mitochondria Triggers Apoptosis through the Permeability Transition Pore Independent of Voltage-Dependent Anion Channels. PLoS ONE, 3.","DOI":"10.1371\/journal.pone.0001852"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Liu, Y., Wu, K., Shi, L., Xiang, F., Tao, K., and Wang, G. (2016). Prognostic Significance of the Metabolic Marker Hexokinase-2 in Various Solid Tumors: A Meta-Analysis. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0166230"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2830","DOI":"10.1038\/sj.emboj.7600279","article-title":"Myc-Induced Proliferation and Transformation Require Akt-Mediated Phosphorylation of FoxO Proteins","volume":"23","author":"Bouchard","year":"2004","journal-title":"EMBO J."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.1007\/s10555-021-10012-4","article-title":"Progression and Metastasis of Small Cell Lung Carcinoma: The Role of the PI3K\/Akt\/MTOR Pathway and Metabolic Alterations","volume":"40","author":"Krencz","year":"2021","journal-title":"Cancer Metastasis Rev."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"33895","DOI":"10.1074\/jbc.M204681200","article-title":"The Identification of ATP-Citrate Lyase as a Protein Kinase B (Akt) Substrate in Primary Adipocytes","volume":"277","author":"Berwick","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1021\/bi992159y","article-title":"Phosphorylation of Recombinant Human ATP:Citrate Lyase by CAMP-Dependent Protein Kinase Abolishes Homotropic Allosteric Regulation of the Enzyme by Citrate and Increases the Enzyme Activity. Allosteric Activation of ATP:Citrate Lyase by Phosphorylated Sugars","volume":"39","author":"Potapova","year":"2000","journal-title":"Biochemistry"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1016\/j.cmet.2014.06.004","article-title":"Akt-Dependent Metabolic Reprogramming Regulates Tumor Cell Histone Acetylation","volume":"20","author":"Lee","year":"2014","journal-title":"Cell Metab."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"6465","DOI":"10.1038\/sj.onc.1208802","article-title":"PKB\/Akt Induces Transcription of Enzymes Involved in Cholesterol and Fatty Acid Biosynthesis via Activation of SREBP","volume":"24","author":"Porstmann","year":"2005","journal-title":"Oncogene"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2621","DOI":"10.4161\/cc.7.17.6514","article-title":"PI3-K and GSK-3: Akt-Ing Together with Microtubules","volume":"7","author":"Buttrick","year":"2008","journal-title":"Cell Cycle"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"51999","DOI":"10.1074\/jbc.M405522200","article-title":"Regulatory Role of Glycogen Synthase Kinase 3 for Transcriptional Activity of ADD1\/SREBP1c","volume":"279","author":"Kim","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2466","DOI":"10.1093\/nar\/gkv047","article-title":"Regulation of Mammalian Nucleotide Metabolism and Biosynthesis","volume":"43","author":"Lane","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Villa, E., Ali, E., Sahu, U., and Ben-Sahra, I. (2019). Cancer Cells Tune the Signaling Pathways to Empower de Novo Synthesis of Nucleotides. Cancers, 11.","DOI":"10.3390\/cancers11050688"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1016\/j.molcel.2014.05.028","article-title":"Akt Phosphorylation and Regulation of Transketolase Is a Nodal Point for Amino Acid Control of Purine Synthesis","volume":"55","author":"Saha","year":"2014","journal-title":"Mol. Cell"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/j.molcel.2010.06.022","article-title":"Activation of a Metabolic Gene Regulatory Network Downstream of MTOR Complex 1","volume":"39","author":"Yecies","year":"2010","journal-title":"Mol. Cell"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1002\/biof.1624","article-title":"6-Phosphogluconate Dehydrogenase Fuels Multiple Aspects of Cancer Cells: From Cancer Initiation to Metastasis and Chemoresistance","volume":"46","author":"Sarfraz","year":"2020","journal-title":"BioFactors"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Liu, Y.-C., Li, F., Handler, J., Huang, C.R.L., Xiang, Y., Neretti, N., Sedivy, J.M., Zeller, K.I., and Dang, C.V. (2008). Global Regulation of Nucleotide Biosynthetic Genes by C-Myc. PLoS ONE, 3.","DOI":"10.1371\/journal.pone.0002722"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1323","DOI":"10.1126\/science.1228792","article-title":"Stimulation of de Novo Pyrimidine Synthesis by Growth Signaling Through MTOR and S6K1","volume":"339","author":"Howell","year":"2013","journal-title":"Science"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1126\/science.aad0489","article-title":"MTORC1 Induces Purine Synthesis through Control of the Mitochondrial Tetrahydrofolate Cycle","volume":"351","author":"Hoxhaj","year":"2016","journal-title":"Science"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1926","DOI":"10.1101\/gad.1212704","article-title":"Upstream and Downstream of MTOR","volume":"18","author":"Hay","year":"2004","journal-title":"Genes. Dev."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1038\/nrm2672","article-title":"Molecular Mechanisms of MTOR-Mediated Translational Control","volume":"10","author":"Ma","year":"2009","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1080\/10409238.2021.1934811","article-title":"Cancer Cells Dysregulate PI3K\/AKT\/MTOR Pathway Activation to Ensure Their Survival and Proliferation: Mimicking Them Is a Smart Strategy of Gammaherpesviruses","volume":"56","author":"Cirone","year":"2021","journal-title":"Crit. Rev. Biochem. Mol. Biol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1038\/ncb2152","article-title":"AMPK and MTOR Regulate Autophagy through Direct Phosphorylation of Ulk1","volume":"13","author":"Kim","year":"2011","journal-title":"Nat. Cell Biol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"3312","DOI":"10.1038\/s41467-018-05862-6","article-title":"MTOR-Dependent Phosphorylation Controls TFEB Nuclear Export","volume":"9","author":"Napolitano","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1992","DOI":"10.1091\/mbc.e08-12-1249","article-title":"ULK-Atg13-FIP200 Complexes Mediate MTOR Signaling to the Autophagy Machinery","volume":"20","author":"Jung","year":"2009","journal-title":"Mol. Biol. Cell"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1016\/j.redox.2014.12.003","article-title":"Interplay between ROS and Autophagy in Cancer Cells, from Tumor Initiation to Cancer Therapy","volume":"4","author":"Despouy","year":"2015","journal-title":"Redox Biol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"15790","DOI":"10.1073\/pnas.1521919112","article-title":"MTOR Inhibition Activates Overall Protein Degradation by the Ubiquitin Proteasome System as Well as by Autophagy","volume":"112","author":"Zhao","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"161","DOI":"10.5483\/BMBRep.2022.55.4.032","article-title":"Effects of MTORC1 Inhibition on Proteasome Activity and Levels","volume":"55","author":"Park","year":"2022","journal-title":"BMB Rep."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Mishra, R., Patel, H., Alanazi, S., Kilroy, M.K., and Garrett, J.T. (2021). PI3K Inhibitors in Cancer: Clinical Implications and Adverse Effects. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22073464"},{"key":"ref_65","first-page":"1","article-title":"Ocena Profilu Korzy\u015bci i Ryzyka Leczenia Idelalizybem u Chorych Na Przewlek\u0142\u0105 Bia\u0142aczk\u0119 Limfocytow\u0105 i Ch\u0142oniaki Nie-Hodgkina","volume":"10","author":"Giza","year":"2018","journal-title":"Hematologia"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1391","DOI":"10.1200\/JCO.18.01460","article-title":"Final Results of a Randomized, Phase III Study of Rituximab With or Without Idelalisib Followed by Open-Label Idelalisib in Patients With Relapsed Chronic Lymphocytic Leukemia","volume":"37","author":"Sharman","year":"2019","journal-title":"J. Clin. Oncol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"2849","DOI":"10.1200\/JCO.19.03355","article-title":"ASCEND: Phase III, Randomized Trial of Acalabrutinib Versus Idelalisib Plus Rituximab or Bendamustine Plus Rituximab in Relapsed or Refractory Chronic Lymphocytic Leukemia","volume":"38","author":"Ghia","year":"2020","journal-title":"J. Clin. Oncol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1064","DOI":"10.1038\/s41375-020-01010-6","article-title":"A Phase 1b\/2 Study of Duvelisib in Combination with FCR (DFCR) for Frontline Therapy for Younger CLL Patients","volume":"35","author":"Davids","year":"2021","journal-title":"Leukemia"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1182\/blood-2017-05-786566","article-title":"Duvelisib, a Novel Oral Dual Inhibitor of PI3K-\u03b4,\u03b3, Is Clinically Active in Advanced Hematologic Malignancies","volume":"131","author":"Flinn","year":"2018","journal-title":"Blood"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1325","DOI":"10.1002\/ajh.25634","article-title":"Combination Trial of Duvelisib (IPI-145) with Rituximab or Bendamustine\/Rituximab in Patients with Non-Hodgkin Lymphoma or Chronic Lymphocytic Leukemia","volume":"94","author":"Flinn","year":"2019","journal-title":"Am. J. Hematol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1653","DOI":"10.1080\/10428194.2020.1734594","article-title":"IND.216: A Phase II Study of Buparlisib and Associated Biomarkers, Raptor and P70S6K, in Patients with Relapsed and Refractory Chronic Lymphocytic Leukemia","volume":"61","author":"Assouline","year":"2020","journal-title":"Leuk. Lymphoma"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1002\/ajh.24568","article-title":"Buparlisib, a PI3K Inhibitor, Demonstrates Acceptable Tolerability and Preliminary Activity in a Phase I Trial of Patients with Advanced Leukemias","volume":"92","author":"Ragon","year":"2017","journal-title":"Am. J. Hematol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1002\/ijc.27989","article-title":"The Phosphatidylinositol-3 Kinase I Inhibitor BKM120 Induces Cell Death in B-Chronic Lymphocytic Leukemia Cells In Vitro","volume":"133","author":"Amrein","year":"2013","journal-title":"Int. J. Cancer"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"2817","DOI":"10.1182\/blood.2020007376","article-title":"Phase 2 Study of the Safety and Efficacy of Umbralisib in Patients with CLL Who Are Intolerant to BTK or PI3K\u03b4 Inhibitor Therapy","volume":"137","author":"Mato","year":"2021","journal-title":"Blood"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"e38","DOI":"10.1016\/S2352-3026(18)30196-0","article-title":"Umbralisib in Combination with Ibrutinib in Patients with Relapsed or Refractory Chronic Lymphocytic Leukaemia or Mantle Cell Lymphoma: A Multicentre Phase 1\u20131b Study","volume":"6","author":"Davids","year":"2019","journal-title":"Lancet Haematol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"5332","DOI":"10.1182\/bloodadvances.2021005132","article-title":"Integrated Safety Analysis of Umbralisib, a Dual PI3K\u03b4\/CK1\u03b5 Inhibitor, in Relapsed\/Refractory Lymphoid Malignancies","volume":"5","author":"Davids","year":"2021","journal-title":"Blood Adv."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1016\/S1470-2045(18)30082-2","article-title":"Umbralisib, a Novel PI3K\u03b4 and Casein Kinase-1\u03b5 Inhibitor, in Relapsed or Refractory Chronic Lymphocytic Leukaemia and Lymphoma: An Open-Label, Phase 1, Dose-Escalation, First-in-Human Study","volume":"19","author":"Burris","year":"2018","journal-title":"Lancet Oncol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1111\/bjh.18187","article-title":"Suppression of MYC by PI3K\/AKT\/MTOR Pathway Inhibition in Combination with All-Trans Retinoic Acid Treatment for Therapeutic Gain in Acute Myeloid Leukaemia","volume":"198","author":"Stengel","year":"2022","journal-title":"Br. J. Haematol."},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Campolo, M., and Paterniti, I. (2022). Antioxidants and Anti-Inflammatory Effects in Neurodegenerative Diseases (NDs). Antioxidants, 11.","DOI":"10.3390\/antiox11061172"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"79842","DOI":"10.18632\/oncotarget.13035","article-title":"Synergistic Effects of Selective Inhibitors Targeting the PI3K\/AKT\/MTOR Pathway or NUP214-ABL1 Fusion Protein in Human Acute Lymphoblastic Leukemia","volume":"7","author":"Simioni","year":"2016","journal-title":"Oncotarget"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1796","DOI":"10.1002\/jcp.26135","article-title":"Phosphatidylinositol 3-Kinase Inhibition Potentiates Glucocorticoid Response in B-Cell Acute Lymphoblastic Leukemia","volume":"233","author":"Evangelisti","year":"2018","journal-title":"J. Cell Physiol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"631","DOI":"10.7150\/ijbs.14878","article-title":"In Vitro Antileukemia Activity of ZSTK474 on K562 and Multidrug Resistant K562\/A02 Cells","volume":"12","author":"Zhou","year":"2016","journal-title":"Int. J. Biol. Sci."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"23213","DOI":"10.18632\/oncotarget.15542","article-title":"PI3K Isoform Inhibition Associated with Anti Bcr-Abl Drugs Shows in Vitro Increased Anti-Leukemic Activity in Philadelphia Chromosome-Positive B-Acute Lymphoblastic Leukemia Cell Lines","volume":"8","author":"Ultimo","year":"2017","journal-title":"Oncotarget"},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Mao, B., Zhang, Q., Ma, L., Zhao, D.-S., Zhao, P., and Yan, P. (2022). Overview of Research into MTOR Inhibitors. Molecules, 27.","DOI":"10.3390\/molecules27165295"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1162694","DOI":"10.3389\/fonc.2023.1162694","article-title":"Novel Pharmacological and Dietary Approaches to Target MTOR in B-Cell Acute Lymphoblastic Leukemia","volume":"13","author":"Buono","year":"2023","journal-title":"Front. Oncol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1007\/978-3-319-91442-8_8","article-title":"Everolimus","volume":"Volume 211","author":"Hasskarl","year":"2018","journal-title":"Small Molecules in Oncology"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1654","DOI":"10.3324\/haematol.2018.189514","article-title":"Addition of the Mammalian Target of Rapamycin Inhibitor, Everolimus, to Consolidation Therapy in Acute Myeloid Leukemia: Experience from the UK NCRI AML17 Trial","volume":"103","author":"Burnett","year":"2018","journal-title":"Haematologica"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"e27062","DOI":"10.1002\/pbc.27062","article-title":"Phase I Trial of the MTOR Inhibitor Everolimus in Combination with Multi-Agent Chemotherapy in Relapsed Childhood Acute Lymphoblastic Leukemia","volume":"65","author":"Place","year":"2018","journal-title":"Pediatr. Blood Cancer"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"2704","DOI":"10.1158\/1078-0432.CCR-14-2888","article-title":"A Phase I\/II Study of the MTOR Inhibitor Everolimus in Combination with HyperCVAD Chemotherapy in Patients with Relapsed\/Refractory Acute Lymphoblastic Leukemia","volume":"21","author":"Daver","year":"2015","journal-title":"Clin. Cancer Res."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1135","DOI":"10.1007\/s11357-020-00274-1","article-title":"Effect of Rapamycin on Aging and Age-Related Diseases\u2014Past and Future","volume":"43","author":"Selvarani","year":"2021","journal-title":"Geroscience"},{"key":"ref_91","first-page":"813","article-title":"Sirolimus and MTOR Inhibitors: A Review of Side Effects and Specific Management in Solid Organ Transplantation","volume":"42","author":"Nguyen","year":"2019","journal-title":"Drug Saf."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1007\/s10637-018-0585-x","article-title":"Sirolimus Enhances Remission Induction in Patients with High Risk Acute Myeloid Leukemia and MTORC1 Target Inhibition","volume":"36","author":"Kasner","year":"2018","journal-title":"Investig. New Drugs"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1002\/ajh.25333","article-title":"A Randomized Trial of Three Novel Regimens for Recurrent Acute Myeloid Leukemia Demonstrates the Continuing Challenge of Treating This Difficult Disease","volume":"94","author":"Litzow","year":"2019","journal-title":"Am. J. Hematol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1111\/bjh.14569","article-title":"A Phase 1 Trial of Temsirolimus and Intensive Re-Induction Chemotherapy for 2nd or Greater Relapse of Acute Lymphoblastic Leukaemia: A Children\u2019s Oncology Group Study (ADVL1114)","volume":"177","author":"Rheingold","year":"2017","journal-title":"Br. J. Haematol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1111\/j.1365-2141.2011.08940.x","article-title":"Temsirolimus, an MTOR Inhibitor, in Combination with Lower-Dose Clofarabine as Salvage Therapy for Older Patients with Acute Myeloid Leukaemia: Results of a Phase II GIMEMA Study (AML-1107)","volume":"156","author":"Amadori","year":"2012","journal-title":"Br. J. Haematol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"673213","DOI":"10.3389\/fonc.2021.673213","article-title":"Efficacy of a Novel Bi-Steric MTORC1 Inhibitor in Models of B-Cell Acute Lymphoblastic Leukemia","volume":"11","author":"Lee","year":"2021","journal-title":"Front. Oncol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1021\/acs.jmedchem.2c01658","article-title":"Discovery of RMC-5552, a Selective Bi-Steric Inhibitor of MTORC1, for the Treatment of MTORC1-Activated Tumors","volume":"66","author":"Burnett","year":"2023","journal-title":"J. Med. Chem."},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Gao, H., Li, Z., Wang, K., Zhang, Y., Wang, T., Wang, F., and Xu, Y. (2023). Design, Synthesis, and Biological Evaluation of Sulfonamide Methoxypyridine Derivatives as Novel PI3K\/MTOR Dual Inhibitors. Pharmaceuticals, 16.","DOI":"10.3390\/ph16030461"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1182\/blood-2016-05-707653","article-title":"Potent Efficacy of Combined PI3K\/MTOR and JAK or ABL Inhibition in Murine Xenograft Models of Ph-like Acute Lymphoblastic Leukemia","volume":"129","author":"Tasian","year":"2017","journal-title":"Blood"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"5119","DOI":"10.1038\/onc.2016.41","article-title":"Aberrant Activation of the PI3K\/MTOR Pathway Promotes Resistance to Sorafenib in AML","volume":"35","author":"Lindblad","year":"2016","journal-title":"Oncogene"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.canlet.2017.01.035","article-title":"The Dual Specificity PI3K\/MTOR Inhibitor PKI-587 Displays Efficacy against T-Cell Acute Lymphoblastic Leukemia (T-ALL)","volume":"392","author":"Gazi","year":"2017","journal-title":"Cancer Lett."},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"Lang, F., Wunderle, L., Badura, S., Schleyer, E., Br\u00fcggemann, M., Serve, H., Schnittger, S., G\u00f6kbuget, N., Pfeifer, H., and Wagner, S. (2020). A Phase I Study of a Dual PI3-Kinase\/MTOR Inhibitor BEZ235 in Adult Patients with Relapsed or Refractory Acute Leukemia. BMC Pharmacol. Toxicol., 21.","DOI":"10.1186\/s40360-020-00446-x"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"301","DOI":"10.3892\/mmr.2021.11940","article-title":"Dual PI3K\/MTOR Inhibitor NVP-BEZ235 Decreases the Proliferation of Doxorubicin-resistant K562 Cells","volume":"23","author":"Li","year":"2021","journal-title":"Mol. Med. Rep."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1038\/aps.2016.121","article-title":"The PI3K\/MTOR Dual Inhibitor BEZ235 Suppresses Proliferation and Migration and Reverses Multidrug Resistance in Acute Myeloid Leukemia","volume":"38","author":"Deng","year":"2017","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"828","DOI":"10.1038\/leu.2014.305","article-title":"Dual PI3K\/MTOR Inhibition Shows Antileukemic Activity in MLL-Rearranged Acute Myeloid Leukemia","volume":"29","author":"Metzeler","year":"2015","journal-title":"Leukemia"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1158\/1078-0432.CCR-15-0114","article-title":"Modulation of Glucocorticoid Resistance in Pediatric T-Cell Acute Lymphoblastic Leukemia by Increasing BIM Expression with the PI3K\/MTOR Inhibitor BEZ235","volume":"22","author":"Hall","year":"2016","journal-title":"Clin. Cancer Res."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"7933","DOI":"10.2147\/CMAR.S204472","article-title":"Protective Autophagy or Autophagic Death: Effects of BEZ235 on Chronic Myelogenous Leukemia","volume":"11","author":"Xin","year":"2019","journal-title":"Cancer Manag. Res."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.2147\/DDDT.S132092","article-title":"Efficacy of the Dual PI3K and MTOR Inhibitor NVP-BEZ235 in Combination with Imatinib Mesylate against Chronic Myelogenous Leukemia Cell Lines","volume":"11","author":"Xin","year":"2017","journal-title":"Drug Des. Develop. Ther."},{"key":"ref_109","first-page":"5311","article-title":"Effects of NVP-BEZ235, a Dual Phosphatidylinositol 3-Kinase\/Mammalian Target of Rapamycin Inhibitor, on HTLV-1-Infected T-Cell Lines","volume":"15","author":"Ishikawa","year":"2018","journal-title":"Oncol. Lett."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"1005659","DOI":"10.3389\/fonc.2022.1005659","article-title":"Mechanisms of Venetoclax Resistance and Solutions","volume":"12","author":"Liu","year":"2022","journal-title":"Front. Oncol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"2026","DOI":"10.1080\/10428194.2017.1283032","article-title":"Pathways and Mechanisms of Venetoclax Resistance","volume":"58","author":"Bose","year":"2017","journal-title":"Leuk. Lymphoma"},{"key":"ref_112","doi-asserted-by":"crossref","unstructured":"Dumble, M., Crouthamel, M.-C., Zhang, S.-Y., Schaber, M., Levy, D., Robell, K., Liu, Q., Figueroa, D.J., Minthorn, E.A., and Seefeld, M.A. (2014). Discovery of Novel AKT Inhibitors with Enhanced Anti-Tumor Effects in Combination with the MEK Inhibitor. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0100880"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1016\/j.clml.2019.03.015","article-title":"Oral MEK 1\/2 Inhibitor Trametinib in Combination with AKT Inhibitor GSK2141795 in Patients with Acute Myeloid Leukemia with RAS Mutations: A Phase II Study","volume":"19","author":"Ragon","year":"2019","journal-title":"Clin. Lymphoma Myeloma Leuk."},{"key":"ref_114","first-page":"157","article-title":"Zydelig (Idelalisib): First-in-Class PI3 Kinase Inhibitor Approved for the Treatment of 3 Hematologic Malignancies","volume":"8","author":"Raedler","year":"2015","journal-title":"Am. Health Drug Benefits"},{"key":"ref_115","doi-asserted-by":"crossref","unstructured":"(2018). Duvelisib Approved for Leukemia, Lymphoma. Cancer Discov., 8, OF4.","DOI":"10.1158\/2159-8290.CD-NB2018-137"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"e100","DOI":"10.1016\/S2352-3026(18)30216-3","article-title":"Tolerability and Activity of Ublituximab, Umbralisib, and Ibrutinib in Patients with Chronic Lymphocytic Leukaemia and Non-Hodgkin Lymphoma: A Phase 1 Dose Escalation and Expansion Trial","volume":"6","author":"Nastoupil","year":"2019","journal-title":"Lancet Haematol."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"3958","DOI":"10.1158\/1078-0432.CCR-22-0964","article-title":"Adding Umbralisib and Ublituximab (U2) to Ibrutinib in Patients with CLL: A Phase II Study of an MRD-Driven Approach","volume":"28","author":"Roeker","year":"2022","journal-title":"Clin. Cancer Res."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"1479","DOI":"10.1038\/leu.2013.17","article-title":"A Phase Ib GOELAMS Study of the MTOR Inhibitor RAD001 in Association with Chemotherapy for AML Patients in First Relapse","volume":"27","author":"Park","year":"2013","journal-title":"Leukemia"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"1585","DOI":"10.3109\/10428194.2015.1113280","article-title":"Treatment of Relapsed\/Refractory Chronic Lymphocytic Leukemia\/Small Lymphocytic Lymphoma with Everolimus (RAD001) and Alemtuzumab: A Phase I\/II Study","volume":"57","author":"Zent","year":"2016","journal-title":"Leuk. Lymphoma"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"5165","DOI":"10.1158\/1078-0432.CCR-06-0764","article-title":"Phase I\/II Study of the Mammalian Target of Rapamycin Inhibitor Everolimus (RAD001) in Patients with Relapsed or Refractory Hematologic Malignancies","volume":"12","author":"Yee","year":"2006","journal-title":"Clin. Cancer Res."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"2201","DOI":"10.1002\/cncr.25005","article-title":"The Treatment of Recurrent\/Refractory Chronic Lymphocytic Leukemia\/Small Lymphocytic Lymphoma (CLL) with Everolimus Results in Clinical Responses and Mobilization of CLL Cells into the Circulation","volume":"116","author":"Zent","year":"2010","journal-title":"Cancer"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"1622","DOI":"10.1016\/j.leukres.2013.09.002","article-title":"A Phase I Study of Decitabine and Rapamycin in Relapsed\/Refractory AML","volume":"37","author":"Liesveld","year":"2013","journal-title":"Leuk. Res."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"106749","DOI":"10.1016\/j.leukres.2021.106749","article-title":"A Phase II Study of Sequential Decitabine and Rapamycin in Acute Myelogenous Leukemia","volume":"112","author":"Liesveld","year":"2022","journal-title":"Leuk. Res."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"10512","DOI":"10.1200\/JCO.2020.38.15_suppl.10512","article-title":"Temsirolimus Combined with Etoposide and Cyclophosphamide for Relapsed\/Refractory Acute Lymphoblastic Leukemia: Therapeutic Advances in Childhood Leukemia Consortium (TACL 2014-001) Trial","volume":"38","author":"Rheingold","year":"2020","journal-title":"J. Clin. Oncol."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"10029","DOI":"10.1200\/jco.2015.33.15_suppl.10029","article-title":"Temsirolimus and Intensive Re-Induction Chemotherapy for 2nd or Greater Relapse of Acute Lymphoblastic Leukemia (ALL): A Children\u2019s Oncology Group Study","volume":"33","author":"Rheingold","year":"2015","journal-title":"J. Clin. Oncol."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"4740","DOI":"10.1200\/JCO.2010.29.2813","article-title":"Temsirolimus Has Activity in Non\u2013Mantle Cell Non-Hodgkin\u2019s Lymphoma Subtypes: The University of Chicago Phase II Consortium","volume":"28","author":"Smith","year":"2010","journal-title":"J. Clin. 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