Targeting the liver kinase B1/AMP-activated protein kinase pathway as a therapeutic strategy for hematological malignancies

Bibliography

• Hardie DG. AMP-activated protein kinase: an energy sensor that regulates all aspects of cell function. Genes Dev 2011;25:1895-908
   PubMed Web of Science ®Google Scholar
• Woods A, Johnstone SR, Dickerson K, LKB1 is the upstream kinase in the AMP-activated protein kinase cascade. Curr Biol 2003;13:2004-8
   PubMed Web of Science ®Google Scholar
• Hemminki A, Markie D, Tomlinson I, A serine/threonine kinase gene defective in Peutz-Jeghers syndrome. Nature 1998;391:184-7
   PubMed Web of Science ®Google Scholar
• van Veelen W, Korsse SE, van de Laar L, Peppelenbosch MP. The long and winding road to rational treatment of cancer associated with LKB1/AMPK/TSC/mTORC1 signaling. Oncogene 2011;30:2289-303
   PubMed Web of Science ®Google Scholar
• Sanchez-Cespedes M, Parrella P, Esteller M, Inactivation of LKB1/STK11 is a common event in adenocarcinomas of the lung. Cancer Res 2002;62:3659-62
   PubMed Web of Science ®Google Scholar
• Wingo SN, Gallardo TD, Akbay EA, Somatic LKB1 mutations promote cervical cancer progression. PLoS ONE 2009;4:e5137
   PubMed Web of Science ®Google Scholar
• Hawley SA, Boudeau J, Reid JL, Complexes between the LKB1 tumor suppressor, STRAD alpha/beta and MO25 alpha/beta are upstream kinases in the AMP-activated protein kinase cascade. J Biol 2003;2:28
   PubMedGoogle Scholar
• Baas AF, Boudeau J, Sapkota GP, Activation of the tumour suppressor kinase LKB1 by the STE20-like pseudokinase STRAD. EMBO J 2003;22:3062-72
   PubMed Web of Science ®Google Scholar
• Boudeau J, Baas AF, Deak M, MO25alpha/beta interact with STRADalpha/beta enhancing their ability to bind, activate and localize LKB1 in the cytoplasm. EMBO J 2003;22:5102-14
   PubMed Web of Science ®Google Scholar
• Campas C, Lopez JM, Santidrian AF, Acadesine activates AMPK and induces apoptosis in B-cell chronic lymphocytic leukemia cells but not in T lymphocytes. Blood 2003;101:3674-80
   PubMed Web of Science ®Google Scholar
• Baumann P, Mandl-Weber S, Emmerich B, Activation of adenosine monophosphate activated protein kinase inhibits growth of multiple myeloma cells. Exp Cell Res 2007;313:3592-603
   PubMed Web of Science ®Google Scholar
• Drakos E, Atsaves V, Li J, Stabilization and activation of p53 downregulates mTOR signaling through AMPK in mantle cell lymphoma. Leukemia 2009;23:784-90
   PubMed Web of Science ®Google Scholar
• Puissant A, Robert G, Fenouille N, Resveratrol promotes autophagic cell death in chronic myelogenous leukemia cells via JNK-mediated p62/SQSTM1 expression and AMPK activation. Cancer Res 2010;70:1042-52
   PubMed Web of Science ®Google Scholar
• Green AS, Chapuis N, Maciel TT, The LKB1/AMPK signaling pathway has tumor suppressor activity in acute myeloid leukemia through the repression of mTOR-dependent oncogenic mRNA translation. Blood 2010;116:4262-73
   PubMed Web of Science ®Google Scholar
• Grimaldi C, Chiarini F, Tabellini G, AMP-dependent kinase/mammalian target of rapamycin complex 1 signaling in T-cell acute lymphoblastic leukemia: therapeutic implications. Leukemia 2010;26:91-100
   Google Scholar
• Inoki K, Kim J, Guan KL. AMPK and mTOR in cellular energy homeostasis and drug targets. Annu Rev Pharmacol Toxicol 2012;52:381-400
   PubMed Web of Science ®Google Scholar
• Hardie DG. AMP-activated/SNF1 protein kinases: conserved guardians of cellular energy. Nat Rev Mol Cell Biol 2007;8:774-85
   PubMed Web of Science ®Google Scholar
• Veech RL, Lawson JW, Cornell NW, Krebs HA. Cytosolic phosphorylation potential. J Biol Chem 1979;254:6538-47
   PubMed Web of Science ®Google Scholar
• Hellsten Y, Richter EA, Kiens B, Bangsbo J. AMP deamination and purine exchange in human skeletal muscle during and after intense exercise. J Physiol 1999;520:909-20
   PubMed Web of Science ®Google Scholar
• Hawley SA, Selbert MA, Goldstein EG, 5'-AMP activates the AMP-activated protein kinase cascade, and Ca2+/calmodulin activates the calmodulin-dependent protein kinase I cascade, via three independent mechanisms. J Biol Chem 1995;270:27186-91
   PubMed Web of Science ®Google Scholar
• Xiao B, Sanders MJ, Underwood E, Structure of mammalian AMPK and its regulation by ADP. Nature 2011;472:230-3
   PubMed Web of Science ®Google Scholar
• Hawley SA, Pan DA, Mustard KJ, Calmodulin-dependent protein kinase kinase-beta is an alternative upstream kinase for AMP-activated protein kinase. Cell Metab 2005;2:9-19
   PubMed Web of Science ®Google Scholar
• Hong SP, Leiper FC, Woods A, Activation of yeast Snf1 and mammalian AMP-activated protein kinase by upstream kinases. Proc Natl Acad Sci USA 2003;100:8839-43
   PubMed Web of Science ®Google Scholar
• Momcilovic M, Hong SP, Carlson M. Mammalian TAK1 activates Snf1 protein kinase in yeast and phosphorylates AMP-activated protein kinase in vitro. J Biol Chem 2006;281:25336-43
   PubMed Web of Science ®Google Scholar
• Tamas P, Hawley SA, Clarke RG, Regulation of the energy sensor AMP-activated protein kinase by antigen receptor and Ca2+ in T lymphocytes. J Exp Med 2006;203:1665-70
   PubMed Web of Science ®Google Scholar
• Marsin AS, Bertrand L, Rider MH, Phosphorylation and activation of heart PFK-2 by AMPK has a role in the stimulation of glycolysis during ischaemia. Curr Biol 2000;10:1247-55
   PubMed Web of Science ®Google Scholar
• Davies SP, Sim AT, Hardie DG. Location and function of three sites phosphorylated on rat acetyl-CoA carboxylase by the AMP-activated protein kinase. Eur J Biochem 1990;187:183-90
   PubMedGoogle Scholar
• Munday MR. Regulation of mammalian acetyl-CoA carboxylase. Biochem Soc Trans 2002;30:1059-64
   PubMed Web of Science ®Google Scholar
• Saggerson D. Malonyl-CoA, a key signaling molecule in mammalian cells. Annu Rev Nutr 2008;28:253-72
   PubMed Web of Science ®Google Scholar
• Carling D, Clarke PR, Zammit VA, Hardie DG. Purification and characterization of the AMP-activated protein kinase. Copurification of acetyl-CoA carboxylase kinase and 3-hydroxy-3-methylglutaryl-CoA reductase kinase activities. Eur J Biochem 1989;186:129-36
   PubMedGoogle Scholar
• Koo SH, Flechner L, Qi L, The CREB coactivator TORC2 is a key regulator of fasting glucose metabolism. Nature 2005;437:1109-11
   PubMed Web of Science ®Google Scholar
• Jager S, Handschin C, St-Pierre J, Spiegelman BM. AMP-activated protein kinase (AMPK) action in skeletal muscle via direct phosphorylation of PGC-1alpha. Proc Natl Acad Sci USA 2007;104:12017-22
   PubMed Web of Science ®Google Scholar
• Chen S, Murphy J, Toth R, Complementary regulation of TBC1D1 and AS160 by growth factors, insulin and AMPK activators. Biochem J 2008;409:449-59
   PubMed Web of Science ®Google Scholar
• Geraghty KM, Chen S, Harthill JE, Regulation of multisite phosphorylation and 14-3-3 binding of AS160 in response to IGF-1, EGF, PMA and AICAR. Biochem J 2007;407:231-41
   PubMed Web of Science ®Google Scholar
• Mihaylova MM, Vasquez DS, Ravnskjaer K, Class IIa histone deacetylases are hormone-activated regulators of FOXO and mammalian glucose homeostasis. Cell 2011;145:607-21
   PubMed Web of Science ®Google Scholar
• McGee SL, van Denderen BJ, Howlett KF, AMP-activated protein kinase regulates GLUT4 transcription by phosphorylating histone deacetylase 5. Diabetes 2008;57:860-7
   PubMed Web of Science ®Google Scholar
• Funai K, Cartee GD. Inhibition of contraction-stimulated AMP-activated protein kinase inhibits contraction-stimulated increases in PAS-TBC1D1 and glucose transport without altering PAS-AS160 in rat skeletal muscle. Diabetes 2009;58:1096-104
   Google Scholar
• Lee JO, Lee SK, Jung JH, Metformin induces Rab4 through AMPK and modulates GLUT4 translocation in skeletal muscle cells. J Cell Physiol 2011;226:974-81
   PubMed Web of Science ®Google Scholar
• Ventura-Clapier R, Garnier A, Veksler V. Transcriptional control of mitochondrial biogenesis: the central role of PGC-1alpha. Cardiovasc Res 2008;79:208-17
   PubMed Web of Science ®Google Scholar
• Canto C, Jiang LQ, Deshmukh AS, Interdependence of AMPK and SIRT1 for metabolic adaptation to fasting and exercise in skeletal muscle. Cell Metab 2010;11:213-19
   PubMed Web of Science ®Google Scholar
• Horman S, Browne G, Krause U, Activation of AMP-activated protein kinase leads to the phosphorylation of elongation factor 2 and an inhibition of protein synthesis. Curr Biol 2002;12:1419-23
   PubMed Web of Science ®Google Scholar
• Kim J, Kundu M, Viollet B, Guan KL. AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1. Nat Cell Biol 2011;13:132-41
   PubMed Web of Science ®Google Scholar
• Mizushima N. The role of the Atg1/ULK1 complex in autophagy regulation. Curr Opin Cell Biol 2011;22:132-9
   Google Scholar
• Zoncu R, Efeyan A, Sabatini DM. mTOR: from growth signal integration to cancer, diabetes and ageing. Nat Rev Mol Cell Biol 2011;12:21-35
   PubMed Web of Science ®Google Scholar
• Dowling RJ, Topisirovic I, Fonseca BD, Sonenberg N. Dissecting the role of mTOR: lessons from mTOR inhibitors. Biochim Biophys Acta 2010;1804:433-9
   PubMed Web of Science ®Google Scholar
• Hornberger TA, Sukhija KB, Wang XR, Chien S. mTOR is the rapamycin-sensitive kinase that confers mechanically-induced phosphorylation of the hydrophobic motif site Thr(389) in p70(S6k). FEBS Lett 2007;581:4562-6
   Google Scholar
• Keshwani MM, Gao X, Harris TK. Mechanism of PDK1-catalyzed Thr-229 phosphorylation of the S6K1 protein kinase. J Biol Chem 2009;284:22611-24
   PubMed Web of Science ®Google Scholar
• Hutchinson JA, Shanware NP, Chang H, Tibbetts RS. Regulation of ribosomal protein S6 phosphorylation by casein kinase 1 and protein phosphatase 1. J Biol Chem 2011;286:8688-96
   PubMed Web of Science ®Google Scholar
• Kroczynska B, Kaur S, Katsoulidis E, Interferon-dependent engagement of eukaryotic initiation factor 4B via S6 kinase (S6K) and ribosomal protein S6K-mediated signals. Mol Cell Biol 2009;29:2865-75
   PubMed Web of Science ®Google Scholar
• Schmid T, Jansen AP, Baker AR, Translation inhibitor Pdcd4 is targeted for degradation during tumor promotion. Cancer Res 2008;68:1254-60
   PubMed Web of Science ®Google Scholar
• Fiesel FC, Weber SS, Supper J, TDP-43 regulates global translational yield by splicing of exon junction complex component SKAR. Nucleic Acids Res 2012;40:2668-82
   Google Scholar
• Wang X, Li W, Williams M, Regulation of elongation factor 2 kinase by p90(RSK1) and p70 S6 kinase. EMBO J 2001;20:4370-9
   PubMed Web of Science ®Google Scholar
• Blagden SP, Willis AE. The biological and therapeutic relevance of mRNA translation in cancer. Nat Rev Clin Oncol 2011;8:280-91
   PubMed Web of Science ®Google Scholar
• Lee T, Pelletier J. Eukaryotic initiation factor 4F: a vulnerability of tumor cells. Future Med Chem 2012;4:19-31
   Google Scholar
• Martelli AM, Evangelisti C, Chappell W, Targeting the translational apparatus to improve leukemia therapy: roles of the PI3K/PTEN/Akt/mTOR pathway. Leukemia 2011;25:1064-79
   PubMed Web of Science ®Google Scholar
• Tamburini J, Green AS, Chapuis N, Targeting translation in acute myeloid leukemia: a new paradigm for therapy? Cell Cycle 2009;8:3893-9
   PubMed Web of Science ®Google Scholar
• Diaz-Troya S, Perez-Perez ME, Florencio FJ, Crespo JL. The role of TOR in autophagy regulation from yeast to plants and mammals. Autophagy 2008;4:851-65
   PubMed Web of Science ®Google Scholar
• Alers S, Loffler AS, Wesselborg S, Stork B. Role of AMPK-mTOR-Ulk1/2 in the regulation of autophagy: cross talk, shortcuts, and feedbacks. Mol Cell Biol 2012;32:2-11
   PubMed Web of Science ®Google Scholar
• Manning BD, Tee AR, Logsdon MN, Identification of the tuberous sclerosis complex-2 tumor suppressor gene product tuberin as a target of the phosphoinositide 3-kinase/Akt pathway. Mol Cell 2002;10:151-62
   PubMed Web of Science ®Google Scholar
• Bhaskar PT, Hay N. The two TORCs and Akt. Dev Cell 2007;12:487-502
   PubMed Web of Science ®Google Scholar
• Inoki K, Zhu T, Guan KL. TSC2 mediates cellular energy response to control cell growth and survival. Cell 2003;115:577-90
   PubMed Web of Science ®Google Scholar
• Zheng M, Wang YH, Wu XN, Inactivation of Rheb by PRAK-mediated phosphorylation is essential for energy-depletion-induced suppression of mTORC1. Nat Cell Biol 2011;13:263-72
   PubMed Web of Science ®Google Scholar
• Wolff NC, Vega-Rubin-de-Celis S, Xie XJ, Cell-type-dependent regulation of mTORC1 by REDD1 and the tumor suppressors TSC1/TSC2 and LKB1 in response to hypoxia. Mol Cell Biol 2011;31:1870-84
   PubMed Web of Science ®Google Scholar
• Kalender A, Selvaraj A, Kim SY, Metformin, independent of AMPK, inhibits mTORC1 in a rag GTPase-dependent manner. Cell Metab 2010;11:390-401
   PubMed Web of Science ®Google Scholar
• Gwinn DM, Shackelford DB, Egan DF, AMPK phosphorylation of raptor mediates a metabolic checkpoint. Mol Cell 2008;30:214-26
   PubMed Web of Science ®Google Scholar
• Corradetti MN, Inoki K, Bardeesy N, Regulation of the TSC pathway by LKB1: evidence of a molecular link between tuberous sclerosis complex and Peutz-Jeghers syndrome. Genes Dev 2004;18:1533-8
   PubMed Web of Science ®Google Scholar
• Shaw RJ, Bardeesy N, Manning BD, The LKB1 tumor suppressor negatively regulates mTOR signaling. Cancer Cell 2004;6:91-9
   PubMed Web of Science ®Google Scholar
• Carretero J, Medina PP, Blanco R, Dysfunctional AMPK activity, signalling through mTOR and survival in response to energetic stress in LKB1-deficient lung cancer. Oncogene 2007;26:1616-25
   PubMed Web of Science ®Google Scholar
• Ikeda Y, Sato K, Pimentel DR, Cardiac-specific deletion of LKB1 leads to hypertrophy and dysfunction. J Biol Chem 2009;284:35839-49
   PubMed Web of Science ®Google Scholar
• Shackelford DB, Shaw RJ. The LKB1-AMPK pathway: metabolism and growth control in tumour suppression. Nat Rev Cancer 2009;9:563-75
   PubMed Web of Science ®Google Scholar
• El-Kaissi S, Sherbeeni S. Pharmacological management of type 2 diabetes mellitus: an update. Curr Diabetes Rev 2011;7:392-405
   PubMedGoogle Scholar
• Memmott RM, Dennis PA. LKB1 and mammalian target of rapamycin as predictive factors for the anticancer efficacy of metformin. J Clin Oncol 2009;27:e226
   PubMed Web of Science ®Google Scholar
• Dowling RJ, Zakikhani M, Fantus IG, Metformin inhibits mammalian target of rapamycin-dependent translation initiation in breast cancer cells. Cancer Res 2007;67:10804-12
   PubMed Web of Science ®Google Scholar
• Hawley SA, Ross FA, Chevtzoff C, Use of cells expressing gamma subunit variants to identify diverse mechanisms of AMPK activation. Cell Metab 2010;11:554-65
   PubMed Web of Science ®Google Scholar
• Kim E, Goraksha-Hicks P, Li L, Regulation of TORC1 by Rag GTPases in nutrient response. Nat Cell Biol 2008;10:935-45
   PubMed Web of Science ®Google Scholar
• Sancak Y, Peterson TR, Shaul YD, The Rag GTPases bind raptor and mediate amino acid signaling to mTORC1. Science 2008;320:1496-501
   PubMed Web of Science ®Google Scholar
• Crofford OB. Metformin. N Engl J Med 1995;333:588-9
   PubMed Web of Science ®Google Scholar
• Mudaliar S, Henry RR. New oral therapies for type 2 diabetes mellitus: the glitazones or insulin sensitizers. Annu Rev Med 2001;52:239-57
   PubMed Web of Science ®Google Scholar
• Fryer LG, Parbu-Patel A, Carling D. The Anti-diabetic drugs rosiglitazone and metformin stimulate AMP-activated protein kinase through distinct signaling pathways. J Biol Chem 2002;277:25226-32
   PubMed Web of Science ®Google Scholar
• Han S, Roman J. Rosiglitazone suppresses human lung carcinoma cell growth through PPARgamma-dependent and PPARgamma-independent signal pathways. Mol Cancer Ther 2006;5:430-7
   PubMed Web of Science ®Google Scholar
• LeBrasseur NK, Kelly M, Tsao TS, Thiazolidinediones can rapidly activate AMP-activated protein kinase in mammalian tissues. Am J Physiol 2006;291:E175-81
   PubMed Web of Science ®Google Scholar
• Simo R, Rodriguez A, Caveda E. Different effects of thiazolidinediones on cardiovascular risk in patients with type 2 diabetes mellitus: pioglitazone versus rosiglitazone. Curr Drug Saf 2010;5:234-44
   PubMedGoogle Scholar
• Sullivan JE, Brocklehurst KJ, Marley AE, Inhibition of lipolysis and lipogenesis in isolated rat adipocytes with AICAR, a cell-permeable activator of AMP-activated protein kinase. FEBS Lett 1994;353:33-6
   PubMed Web of Science ®Google Scholar
• Corton JM, Gillespie JG, Hawley SA, Hardie DG. 5-aminoimidazole-4-carboxamide ribonucleoside. A specific method for activating AMP-activated protein kinase in intact cells? Eur J Biochem 1995;229:558-65
   PubMedGoogle Scholar
• Day P, Sharff A, Parra L, Structure of a CBS-domain pair from the regulatory gamma1 subunit of human AMPK in complex with AMP and ZMP. Acta Crystallogr D Biol Crystallogr 2007;63:587-96
   PubMedGoogle Scholar
• Cool B, Zinker B, Chiou W, Identification and characterization of a small molecule AMPK activator that treats key components of type 2 diabetes and the metabolic syndrome. Cell Metab 2006;3:403-16
   PubMed Web of Science ®Google Scholar
• Turner N, Li JY, Gosby A, Berberine and its more biologically available derivative, dihydroberberine, inhibit mitochondrial respiratory complex I: a mechanism for the action of berberine to activate AMP-activated protein kinase and improve insulin action. Diabetes 2008;57:1414-18
   PubMed Web of Science ®Google Scholar
• Gledhill JR, Montgomery MG, Leslie AG, Walker JE. Mechanism of inhibition of bovine F1-ATPase by resveratrol and related polyphenols. Proc Natl Acad Sci USA 2007;104:13632-7
   PubMed Web of Science ®Google Scholar
• Evans JM, Donnelly LA, Emslie-Smith AM, Metformin and reduced risk of cancer in diabetic patients. BMJ 2005;330:1304-5
   PubMed Web of Science ®Google Scholar
• Bowker SL, Majumdar SR, Veugelers P, Johnson JA. Increased cancer-related mortality for patients with type 2 diabetes who use sulfonylureas or insulin: response to Farooki and Schneider. Diabetes Care 2006;29:1990-1
   PubMed Web of Science ®Google Scholar
• Murtola TJ, Tammela TL, Lahtela J, Auvinen A. Antidiabetic medication and prostate cancer risk: a population-based case-control study. Am J Epidemiol 2008;168:925-31
   PubMed Web of Science ®Google Scholar
• Libby G, Donnelly LA, Donnan PT, New users of metformin are at low risk of incident cancer: a cohort study among people with type 2 diabetes. Diabetes Care 2009;32:1620-5
   PubMed Web of Science ®Google Scholar
• Noto H, Goto A, Tsujimoto T, Noda M. Cancer risk in diabetic patients treated with metformin: a systematic review and meta-analysis. PloS One 2012;7:1-9
   Google Scholar
• Gallagher EJ, LeRoith D. Minireview: IGF, Insulin, and cancer. Endocrinology 2011;152:2546-51
   PubMed Web of Science ®Google Scholar
• Calle EE, Kaaks R. Overweight, obesity and cancer: epidemiological evidence and proposed mechanisms. Nat Rev Cancer 2004;4:579-91
   PubMed Web of Science ®Google Scholar
• Yang YX, Hennessy S, Lewis JD. Insulin therapy and colorectal cancer risk among type 2 diabetes mellitus patients. Gastroenterology 2004;127:1044-50
   PubMed Web of Science ®Google Scholar
• Lipscombe LL, Goodwin PJ, Zinman B, Diabetes mellitus and breast cancer: a retrospective population-based cohort study. Breast Cancer Res Treat 2006;98:349-56
   PubMed Web of Science ®Google Scholar
• Lipscombe LL, Goodwin PJ, Zinman B, Increased prevalence of prior breast cancer in women with newly diagnosed diabetes. Breast Cancer Res Treat 2006;98:303-9
   Google Scholar
• Huang X, Wullschleger S, Shpiro N, Important role of the LKB1-AMPK pathway in suppressing tumorigenesis in PTEN-deficient mice. Biochem J 2008;412:211-21
   PubMed Web of Science ®Google Scholar
• Hadad SM, Baker L, Quinlan PR, Histological evaluation of AMPK signalling in primary breast cancer. BMC Cancer 2009;9:307
   PubMedGoogle Scholar
• Horman S, Vertommen D, Heath R, Insulin antagonizes ischemia-induced Thr172 phosphorylation of AMP-activated protein kinase alpha-subunits in heart via hierarchical phosphorylation of Ser485/491. J Biol Chem 2006;281:5335-40
   PubMed Web of Science ®Google Scholar
• Workman P, Clarke PA, Raynaud FI, van Montfort RL. Drugging the PI3 kinome: from chemical tools to drugs in the clinic. Cancer Res 2010;70:2146-57
   PubMed Web of Science ®Google Scholar
• Ben Sahra I, Le Marchand-Brustel Y, Tanti JF, Bost F. Metformin in cancer therapy: a new perspective for an old antidiabetic drug? Mol Cancer Ther 2010;9:1092-9
   PubMed Web of Science ®Google Scholar
• Bost F, Sahra IB, Le Marchand-Brustel Y, Tanti JF. Metformin and cancer therapy. Curr Opin Oncol 2012;24:103-8
   PubMed Web of Science ®Google Scholar
• Del Barco S, Vazquez-Martin A, Cufi S, Metformin: multi-faceted protection against cancer. Oncotarget 2011;2:896-917
   PubMed Web of Science ®Google Scholar
• Aljada A, Mousa SA. Metformin and neoplasia: implications and indications. Pharmacol Ther 2012;133:108-15
   PubMed Web of Science ®Google Scholar
• Ma S, Rosen ST. Signal transduction inhibitors in chronic lymphocytic leukemia. Curr Opin Oncol 2011;23:601-8
   PubMed Web of Science ®Google Scholar
• Santidrian AF, Gonzalez-Girones DM, AICAR induces apoptosis independently of AMPK and p53 through up-regulation of the BH3-only proteins BIM and NOXA in chronic lymphocytic leukemia cells. Blood 2010;116:3023-32
   PubMed Web of Science ®Google Scholar
• Adams JM, Cory S. The Bcl-2 apoptotic switch in cancer development and therapy. Oncogene 2007;26:1324-37
   PubMed Web of Science ®Google Scholar
• Robert G, Ben Sahra I, Puissant A, Acadesine kills chronic myelogenous leukemia (CML) cells through PKC-dependent induction of autophagic cell death. PLoS One 2009;4:e7889
   PubMed Web of Science ®Google Scholar
• Hiwase DK, Yeung DT, White DL. Optimizing the selection of kinase inhibitors for chronic myeloid leukemia patients. Expert Rev Hematol 2011;4:285-99
   PubMed Web of Science ®Google Scholar
• Vakana E, Altman JK, Glaser H, Antileukemic effects of AMPK activators on BCR-ABL-expressing cells. Blood 2011;118:6399-402
   PubMed Web of Science ®Google Scholar
• Puissant A, Auberger P. AMPK- and p62/SQSTM1-dependent autophagy mediate Resveratrol-induced cell death in chronic myelogenous leukemia. Autophagy 2010;6:655-7
   PubMed Web of Science ®Google Scholar
• Pui CH, Carroll WL, Meshinchi S, Arceci RJ. Biology, risk stratification, and therapy of pediatric acute leukemias: an update. J Clin Oncol 2011;29:551-65
   PubMed Web of Science ®Google Scholar
• Sengupta TK, Leclerc GM, Hsieh-Kinser TT, Cytotoxic effect of 5-aminoimidazole-4-carboxamide-1-beta-4-ribofuranoside (AICAR) on childhood acute lymphoblastic leukemia (ALL) cells: implication for targeted therapy. Mol Cancer 2007;6:46
   PubMed Web of Science ®Google Scholar
• Sengupta S, Peterson TR, Sabatini DM. Regulation of the mTOR complex 1 pathway by nutrients, growth factors, and stress. Mol Cell 2010;40:310-22
   PubMed Web of Science ®Google Scholar
• Tamburini J, Chapuis N, Bardet V, Mammalian target of rapamycin (mTOR) inhibition activates phosphatidylinositol 3-kinase/Akt by up-regulating insulin-like growth factor-1 receptor signaling in acute myeloid leukemia: rationale for therapeutic inhibition of both pathways. Blood 2008;111:379-82
   PubMed Web of Science ®Google Scholar
• Leclerc GM, Leclerc GJ, Fu G, Barredo JC. AMPK-induced activation of Akt by AICAR is mediated by IGF-1R dependent and independent mechanisms in acute lymphoblastic leukemia. J Mol Signal 2010;5:15
   Google Scholar
• Bhojwani D, Pei D, Sandlund JT, ETV6-RUNX1-positive childhood acute lymphoblastic leukemia: improved outcome with contemporary therapy. Leukemia 2012;26:265-70
   PubMed Web of Science ®Google Scholar
• Kuznetsov JN, Leclerc GJ, Leclerc GM, Barredo JC. AMPK and Akt determine apoptotic cell death following perturbations of one-carbon metabolism by regulating ER stress in acute lymphoblastic leukemia. Mol Cancer Ther 2011;10:437-47
   Google Scholar
• Park HU, Suy S, Danner M, AMP-activated protein kinase promotes human prostate cancer cell growth and survival. Mol Cancer Ther 2009;8:733-41
   PubMed Web of Science ®Google Scholar
• Beckers A, Organe S, Timmermans L, Methotrexate enhances the antianabolic and antiproliferative effects of 5-aminoimidazole-4-carboxamide riboside. Mol Cancer Ther 2006;5:2211-17
   PubMed Web of Science ®Google Scholar
• Silva A, Yunes JA, Cardoso BA, PTEN posttranslational inactivation and hyperactivation of the PI3K/Akt pathway sustain primary T cell leukemia viability. J Clin Invest 2008;118:3762-74
   PubMed Web of Science ®Google Scholar
• Mavrakis KJ, Wolfe AL, Oricchio E, Genome-wide RNA-mediated interference screen identifies miR-19 targets in Notch-induced T-cell acute lymphoblastic leukaemia. Nat Cell Biol 2010;12:372-9
   PubMed Web of Science ®Google Scholar
• Campas C, Santidrian AF, Domingo A, Gil J. Acadesine induces apoptosis in B cells from mantle cell lymphoma and splenic marginal zone lymphoma. Leukemia 2005;19:292-4
   PubMed Web of Science ®Google Scholar
• Budanov AV, Karin M. p53 target genes sestrin1 and sestrin2 connect genotoxic stress and mTOR signaling. Cell 2008;134:451-60
   PubMed Web of Science ®Google Scholar
• Iwata M, Graf L, Awaya N, Torok-Storb B. Functional interleukin-7 receptors (IL-7Rs) are expressed by marrow stromal cells: binding of IL-7 increases levels of IL-6 mRNA and secreted protein. Blood 2002;100:1318-25
   PubMed Web of Science ®Google Scholar
• Yan J, Yang H, Wang G, Autophagy augmented by troglitazone is independent of EGFR transactivation and correlated with AMP-activated protein kinase signaling. Autophagy 2010;6:67-73
   PubMed Web of Science ®Google Scholar
• Hadad S, Iwamoto T, Jordan L, Evidence for biological effects of metformin in operable breast cancer: a pre-operative, window-of-opportunity, randomized trial. Breast Cancer Res Treat 2011;128:783-94
   PubMed Web of Science ®Google Scholar
• Ben Sahra I, Laurent K, Loubat A, The antidiabetic drug metformin exerts an antitumoral effect in vitro and in vivo through a decrease of cyclin D1 level. Oncogene 2008;27:3576-86
   PubMed Web of Science ®Google Scholar
• Chapuis N, Tamburini J, Green AS, Dual inhibition of PI3K and mTORC1/2 signaling by NVP-BEZ235 as a new therapeutic strategy for acute myeloid leukemia. Clin Cancer Res 2011;16:5424-35
   Google Scholar
• Evangelisti C, Ricci F, Tazzari P, Targeted inhibition of mTORC1 and mTORC2 by active-site mTOR inhibitors has cytotoxic effects in T-cell acute lymphoblastic leukemia. Leukemia 2011;25:781-91
   PubMed Web of Science ®Google Scholar
• Willems L, Chapuis N, Puissant A, The dual mTORC1 and mTORC2 inhibitor AZD8055 has anti-tumor activity in acute myeloid leukemia. Leukemia 2011; In press; doi 10.1038/leu.2011.339
   Google Scholar
• Brusselmans K, De Schrijver E, Verhoeven G, Swinnen JV. RNA interference-mediated silencing of the acetyl-CoA-carboxylase-alpha gene induces growth inhibition and apoptosis of prostate cancer cells. Cancer Res 2005;65:6719-25
   PubMed Web of Science ®Google Scholar
• Chajes V, Cambot M, Moreau K, Acetyl-CoA carboxylase alpha is essential to breast cancer cell survival. Cancer Res 2006;66:5287-94
   PubMed Web of Science ®Google Scholar
• Pietras EM, Warr MR, Passegue E. Cell cycle regulation in hematopoietic stem cells. J Cell Biol 2011;195:709-20
   PubMed Web of Science ®Google Scholar
• Nakada D, Saunders TL, Morrison SJ. Lkb1 regulates cell cycle and energy metabolism in haematopoietic stem cells. Nature 2010;468:653-8
   PubMed Web of Science ®Google Scholar
• Gurumurthy S, Xie SZ, Alagesan B, The Lkb1 metabolic sensor maintains haematopoietic stem cell survival. Nature 2010;468:659-63
   PubMed Web of Science ®Google Scholar
• Gan B, Hu J, Jiang S, Lkb1 regulates quiescence and metabolic homeostasis of haematopoietic stem cells. Nature 2010;468:701-4
   PubMed Web of Science ®Google Scholar
• Martelli AM, Evangelisti C, Chiarini F, The emerging role of the phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin signaling network in normal myelopoiesis and leukemogenesis. Biochim Biophys Acta 2010;1803:991-1002
   PubMed Web of Science ®Google Scholar
• Misaghian N, Ligresti G, Steelman LS, Targeting the leukemic stem cell: the Holy Grail of leukemia therapy. Leukemia 2009;23:25-42
   PubMed Web of Science ®Google Scholar
• ten Cate B, de Bruyn M, Wei Y, Targeted elimination of leukemia stem cells; a new therapeutic approach in hemato-oncology. Curr Drug Targets 2010;11:95-110
   PubMed Web of Science ®Google Scholar
• Karagounis LG, Hawley JA. The 5' adenosine monophosphate-activated protein kinase: regulating the ebb and flow of cellular energetics. Int J Biochem Cell Biol 2009;41:2360-3
   Google Scholar