Autophagy is dispensable for Kmt2a/Mll-Mllt3/Af9 AML maintenance and anti-leukemic effect of chloroquine

References

• Hara T, Takamura A, Kishi C, Iemura S, Natsume T, Guan JL, Mizushima N. FIP200, a ULK-interacting protein, is required for autophagosome formation in mammalian cells. J Cell Biol 2008; 181:497-510; PMID:18443221; http://dx.doi.org/10.1083/jcb.200712064
   PubMed Web of Science ®Google Scholar
• Jung CH, Jun CB, Ro SH, Kim YM, Otto NM, Cao J, Kundu M, Kim DH. ULK-Atg13-FIP200 complexes mediate mTOR signaling to the autophagy machinery. Mol Biol Cell 2009; 20:1992-2003; PMID:19225151; http://dx.doi.org/10.1091/mbc.E08-12-1249
   PubMed Web of Science ®Google Scholar
• Mercer CA, Kaliappan A, Dennis PB. A novel, human Atg13 binding protein, Atg101, interacts with ULK1 and is essential for macroautophagy. Autophagy 2009; 5:649-62; PMID:19287211; http://dx.doi.org/10.4161/auto.5.5.8249
   PubMed Web of Science ®Google Scholar
• Mizushima N, Kuma A, Kobayashi Y, Yamamoto A, Matsubae M, Takao T, Natsume T, Ohsumi Y, Yoshimori T. Mouse Apg16L, a novel WD-repeat protein, targets to the autophagic isolation membrane with the Apg12-Apg5 conjugate. J Cell Sci 2003; 116:1679-88; PMID:12665549; http://dx.doi.org/10.1242/jcs.00381
   PubMed Web of Science ®Google Scholar
• Kabeya Y, Mizushima N, Ueno T, Yamamoto A, Kirisako T, Noda T, Kominami E, Ohsumi Y, Yoshimori T. LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing. EMBO J 2000; 19:5720-8; PMID:11060023; http://dx.doi.org/10.1093/emboj/19.21.5720
   PubMed Web of Science ®Google Scholar
• Nishida Y, Arakawa S, Fujitani K, Yamaguchi H, Mizuta T, Kanaseki T, Komatsu M, Otsu K, Tsujimoto Y, Shimizu S. Discovery of Atg5/Atg7-independent alternative macroautophagy. Nature 2009; 461:654-8; PMID:19794493; http://dx.doi.org/10.1038/nature08455
   PubMed Web of Science ®Google Scholar
• Chittaranjan S, Bortnik S, Dragowska WH, Xu J, Abeysundara N, Leung A, Go NE, DeVorkin L, Weppler SA, Gelmon K, et al. Autophagy inhibition augments the anticancer effects of epirubicin treatment in anthracycline-sensitive and -resistant triple-negative breast cancer. Clin Cancer Res 2014; 20:3159-73; PMID:24721646; http://dx.doi.org/10.1158/1078-0432.CCR-13-2060
   PubMed Web of Science ®Google Scholar
• Ma XH, Piao SF, Dey S, McAfee Q, Karakousis G, Villanueva J, Hart LS, Levi S, Hu J, Zhang G, et al. Targeting ER stress-induced autophagy overcomes BRAF inhibitor resistance in melanoma. J Clin Invest 2014; 124:1406-17; PMID: 24569374; http://dx.doi.org/10.1172/JCI70454
   PubMed Web of Science ®Google Scholar
• Wang J, Wu GS. Role of autophagy in cisplatin resistance in ovarian cancer cells. J Biol Chem 2014; 289:17163-73; PMID:24794870; http://dx.doi.org/10.1074/jbc.M114.558288
   PubMed Web of Science ®Google Scholar
• Vogl DT, Stadtmauer EA, Tan KS, Heitjan DF, Davis LE, Pontiggia L, Rangwala R, Piao S, Chang YC, Scott EC, et al. Combined autophagy and proteasome inhibition: a phase 1 trial of hydroxychloroquine and bortezomib in patients with relapsed/refractory myeloma. Autophagy 2014; 10:1380-90; PMID:24991834; http://dx.doi.org/10.4161/auto.29264
   PubMed Web of Science ®Google Scholar
• Rangwala R, Chang YC, Hu J, Algazy KM, Evans TL, Fecher LA, Schuchter LM, Torigian DA, Panosian JT, Troxel AB, et al. Combined MTOR and autophagy inhibition: phase I trial of hydroxychloroquine and temsirolimus in patients with advanced solid tumors and melanoma. Autophagy 2014; 10:1391-402; PMID:24991838; http://dx.doi.org/10.4161/auto.29119
   PubMed Web of Science ®Google Scholar
• Rosenfeld MR, Ye X, Supko JG, Desideri S, Grossman SA, Brem S, Mikkelson T, Wang D, Chang YC, Hu J, et al. A phase I/II trial of hydroxychloroquine in conjunction with radiation therapy and concurrent and adjuvant temozolomide in patients with newly diagnosed glioblastoma multiforme. Autophagy 2014; 10:1359-68; PMID:24991840; http://dx.doi.org/10.4161/auto.28984
   PubMed Web of Science ®Google Scholar
• Sotelo J, Briceno E, Lopez-Gonzalez MA. Adding chloroquine to conventional treatment for glioblastoma multiforme: a randomized, double-blind, placebo-controlled trial. Ann Intern Med 2006; 144:337-43; PMID:16520474; http://dx.doi.org/10.7326/0003-4819-144-5-200603070-00008
   PubMed Web of Science ®Google Scholar
• Briceno E, Calderon A, Sotelo J. Institutional experience with chloroquine as an adjuvant to the therapy for glioblastoma multiforme. Surg Neurol 2007; 67:388-91; PMID:17350410; http://dx.doi.org/10.1016/j.surneu.2006.08.080
   PubMed Web of Science ®Google Scholar
• Levy JM, Thorburn A. Targeting autophagy during cancer therapy to improve clinical outcomes. Pharmacol Ther 2011; 131:130-41; PMID:21440002; http://dx.doi.org/10.1016/j.pharmthera.2011.03.009
   PubMed Web of Science ®Google Scholar
• Willems L, Chapuis N, Puissant A, Maciel TT, Green AS, Jacque N, Vignon C, Park S, Guichard S, Herault O, et al. The dual mTORC1 and mTORC2 inhibitor AZD8055 has anti-tumor activity in acute myeloid leukemia. Leukemia 2012; 26:1195-202; PMID:22143671; http://dx.doi.org/10.1038/leu.2011.339
   PubMed Web of Science ®Google Scholar
• Wei Y, Kadia T, Tong W, Zhang M, Jia Y, Yang H, Hu Y, Tambaro FP, Viallet J, O'Brien S, et al. The combination of a histone deacetylase inhibitor with the Bcl-2 homology domain-3 mimetic GX15-070 has synergistic antileukemia activity by activating both apoptosis and autophagy. Clin Cancer Res 2010; 16:3923-32; PMID:20538760; http://dx.doi.org/10.1158/1078-0432.CCR-10-0032
   PubMed Web of Science ®Google Scholar
• Torgersen ML, Engedal N, Boe SO, Hokland P, Simonsen A. Targeting autophagy potentiates the apoptotic effect of histone deacetylase inhibitors in t(8;21) AML cells. Blood 2013; 122:2467-76; PMID:23970379; http://dx.doi.org/10.1182/blood-2013-05-500629
   PubMed Web of Science ®Google Scholar
• Watson AS, Riffelmacher T, Stranks A, Williams O, De Boer J, Cain K, MacFarlane M, McGouran J, Kessler B, Khandwala S, et al. Autophagy limits proliferation and glycolytic metabolism in acute myeloid leukemia. Cell Death Discov 2015; 1: 15008. PMID:26568842; http://dx.doi.org/10.1038/cddiscovery.2015.8
   PubMed Web of Science ®Google Scholar
• Piya S, Kornblau SM, Ruvolo VR, Mu H, Ruvolo PP, McQueen T, Davis RE, Hail N, Jr, Kantarjian H, Andreeff M, et al. Atg7 suppression enhances chemotherapeutic agent sensitivity and overcomes stroma-mediated chemoresistance in acute myeloid leukemia. Blood 2016; 128(9):1260-9; PMID:27268264
   PubMed Web of Science ®Google Scholar
• Mortensen M, Soilleux EJ, Djordjevic G, Tripp R, Lutteropp M, Sadighi-Akha E, Stranks AJ, Glanville J, Knight S, Jacobsen SE, et al. The autophagy protein Atg7 is essential for hematopoietic stem cell maintenance. J Exp Med 2011; 208:455-67; PMID:21339326; http://dx.doi.org/10.1084/jem.20101145
   PubMed Web of Science ®Google Scholar
• Liu F, Lee JY, Wei H, Tanabe O, Engel JD, Morrison SJ, Guan JL. FIP200 is required for the cell-autonomous maintenance of fetal hematopoietic stem cells. Blood 2010; 116:4806-14; PMID:20716775; http://dx.doi.org/10.1182/blood-2010-06-288589
   PubMed Web of Science ®Google Scholar
• Warr MR, Binnewies M, Flach J, Reynaud D, Garg T, Malhotra R, Debnath J, Passegue E. FOXO3A directs a protective autophagy program in haematopoietic stem cells. Nature 2013; 494:323-7; PMID:23389440; http://dx.doi.org/10.1038/nature11895
   PubMed Web of Science ®Google Scholar
• Mortensen M, Ferguson DJ, Edelmann M, Kessler B, Morten KJ, Komatsu M, Simon AK. Loss of autophagy in erythroid cells leads to defective removal of mitochondria and severe anemia in vivo. Proc Natl Acad Sci U S A 2010; 107:832-7; PMID:20080761; http://dx.doi.org/10.1073/pnas.0913170107
   PubMed Web of Science ®Google Scholar
• Gomez-Puerto MC, Folkerts H, Wierenga AT, Schepers K, Schuringa JJ, Coffer PJ, Vellenga E. Autophagy proteins ATG5 and ATG7 are essential for the maintenance of human CD34 hematopoietic stem-progenitor cells. Stem Cells 2016; 34(6):1651-63
   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; PMID:21220611; http://dx.doi.org/10.1200/JCO.2010.30.7405
   PubMed Web of Science ®Google Scholar
• Kishi-Itakura C, Koyama-Honda I, Itakura E, Mizushima N. Ultrastructural analysis of autophagosome organization using mammalian autophagy-deficient cells. J Cell Sci 2014; 127:4089-102; PMID:25052093; http://dx.doi.org/10.1242/jcs.156034
   PubMed Web of Science ®Google Scholar
• Hara T, Nakamura K, Matsui M, Yamamoto A, Nakahara Y, Suzuki-Migishima R, Yokoyama M, Mishima K, Saito I, Okano H, et al. Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice. Nature 2006; 441:885-9; PMID:16625204; http://dx.doi.org/10.1038/nature04724
   PubMed Web of Science ®Google Scholar
• Tal MC, Sasai M, Lee HK, Yordy B, Shadel GS, Iwasaki A. Absence of autophagy results in reactive oxygen species-dependent amplification of RLR signaling. Proc Natl Acad Sci U S A 2009; 106:2770-5; PMID:19196953; http://dx.doi.org/10.1073/pnas.0807694106
   PubMed Web of Science ®Google Scholar
• Miyoshi H, Kozu T, Shimizu K, Enomoto K, Maseki N, Kaneko Y, Kamada N, Ohki M. The t(8;21) translocation in acute myeloid leukemia results in production of an AML1-MTG8 fusion transcript. EMBO J 1993; 12:2715-21; PMID:8334990
   PubMed Web of Science ®Google Scholar
• Altman BJ, Jacobs SR, Mason EF, Michalek RD, MacIntyre AN, Coloff JL, Ilkayeva O, Jia W, He YW, Rathmell JC. Autophagy is essential to suppress cell stress and to allow BCR-Abl-mediated leukemogenesis. Oncogene 2011; 30:1855-67; PMID:21151168; http://dx.doi.org/10.1038/onc.2010.561
   PubMed Web of Science ®Google Scholar
• Maes H, Kuchnio A, Peric A, Moens S, Nys K, De Bock K, Quaegebeur A, Schoors S, Georgiadou M, Wouters J, et al. Tumor vessel normalization by chloroquine independent of autophagy. Cancer Cell 2014; 26:190-206; PMID:25117709; http://dx.doi.org/10.1016/j.ccr.2014.06.025
   PubMed Web of Science ®Google Scholar
• Maycotte P, Aryal S, Cummings CT, Thorburn J, Morgan MJ, Thorburn A. Chloroquine sensitizes breast cancer cells to chemotherapy independent of autophagy. Autophagy 2012; 8:200-12; PMID:22252008; http://dx.doi.org/10.4161/auto.8.2.18554
   PubMed Web of Science ®Google Scholar
• Cambie G, Verdier F, Gaudebout C, Clavier F, Ginsburg H. The pharmacokinetics of chloroquine in healthy and Plasmodium chabaudi-infected mice: implications for chronotherapy. Parasite 1994; 1:219-26; PMID:9140488; http://dx.doi.org/10.1051/parasite/1994013219
   PubMed Web of Science ®Google Scholar
• Rosenfeld MR, Grossman SA, Brem S, Mikkelsen T, Wang D, Piao S, Davis LE, O'Dwyer PJ, Amaravadi RK. Pharmacokinetic analysis and pharmacodynamic evidence of autophagy inhibition in patients with newly diagnosed glioblastoma treated on a phase I trial of hydroxychloroquine in combination with adjuvant temozolomide and radiation (ABTC 0603). J Clin Oncol (Meeting Abstracts) 2010; 28:3086
   Web of Science ®Google Scholar
• McAfee Q, Zhang Z, Samanta A, Levi SM, Ma XH, Piao S, Lynch JP, Uehara T, Sepulveda AR, Davis LE, et al. Autophagy inhibitor Lys05 has single-agent antitumor activity and reproduces the phenotype of a genetic autophagy deficiency. Proc Natl Acad Sci U S A 2012; 109:8253-8; PMID:22566612; http://dx.doi.org/10.1073/pnas.1118193109
   PubMed Web of Science ®Google Scholar
• Zhang L, Zhang S, Yao J, Lowery FJ, Zhang Q, Huang WC, Li P, Li M, Wang X, Zhang C, et al. Microenvironment-induced PTEN loss by exosomal microRNA primes brain metastasis outgrowth. Nature 2015; 527:100-4; PMID:26479035; http://dx.doi.org/10.1038/nature15376
   PubMed Web of Science ®Google Scholar
• Ostrowski M, Carmo NB, Krumeich S, Fanget I, Raposo G, Savina A, Moita CF, Schauer K, Hume AN, Freitas RP, et al. Rab27a and Rab27b control different steps of the exosome secretion pathway. Nat Cell Biol 2010; 12:19-30; sup pp 1-13; PMID:19966785; http://dx.doi.org/10.1038/ncb2000
   PubMed Web of Science ®Google Scholar
• Sehgal AR, Konig H, Johnson DE, Tang D, Amaravadi RK, Boyiadzis M, Lotze MT. You eat what you are: autophagy inhibition as a therapeutic strategy in leukemia. Leukemia 2015; 29:517-25; PMID:25541151; http://dx.doi.org/10.1038/leu.2014.349
   PubMed Web of Science ®Google Scholar
• Evangelisti C, Evangelisti C, Chiarini F, Lonetti A, Buontempo F, Neri LM, McCubrey JA, Martelli AM. Autophagy in acute leukemias: a double-edged sword with important therapeutic implications. Biochim Biophys Acta 2015; 1853:14-26; PMID:25284725; http://dx.doi.org/10.1016/j.bbamcr.2014.09.023
   PubMed Web of Science ®Google Scholar
• Sumitomo Y, Koya J, Kataoka K, Tsuruta-Kishino T, Morita K, Sato T, Kurokawa M. Enhanced autophagy promotes survival of peripheral blast cells from murine acute myeloid leukemia. Blood 2014; 124:2339
   Web of Science ®Google Scholar
• Mandelbaum J, Rollins N, Shah P, Bowman D, Lee JY, Tayber O, Bernard H, LeRoy P, Li P, Koenig E, et al. Identification of a lung cancer cell line deficient in atg7-dependent autophagy. Autophagy 2015: June 19 (Epub ahead of print).; PMID:26090719
   PubMedGoogle Scholar
• Ouyang DY, Xu LH, He XH, Zhang YT, Zeng LH, Cai JY, Ren S. Autophagy is differentially induced in prostate cancer LNCaP, DU145 and PC-3 cells via distinct splicing profiles of ATG5. Autophagy 2013; 9:20-32; PMID:23075929; http://dx.doi.org/10.4161/auto.22397
   PubMed Web of Science ®Google Scholar
• Eng CH, Wang Z, Tkach D, Toral-Barza L, Ugwonali S, Liu S, Fitzgerald SL, George E, Frias E, Cochran N, et al. Macroautophagy is dispensable for growth of KRAS mutant tumors and chloroquine efficacy. Proc Natl Acad Sci U S A 2016; 113:182-7; PMID:26677873; http://dx.doi.org/10.1073/pnas.1515617113
   PubMed Web of Science ®Google Scholar
• Solomon VR, Lee H. Chloroquine and its analogs: a new promise of an old drug for effective and safe cancer therapies. Eur J Pharmacol 2009; 625:220-33; PMID:19836374; http://dx.doi.org/10.1016/j.ejphar.2009.06.063
   PubMed Web of Science ®Google Scholar
• Jensen PB, Sorensen BS, Sehested M, Grue P, Demant EJ, Hansen HH. Targeting the cytotoxicity of topoisomerase II-directed epipodophyllotoxins to tumor cells in acidic environments. Cancer Res 1994; 54:2959-63; PMID:8187081
   PubMed Web of Science ®Google Scholar
• Lee CM, Tannock IF. Inhibition of endosomal sequestration of basic anticancer drugs: influence on cytotoxicity and tissue penetration. Br J Cancer 2006; 94:863-9; PMID:16495919; http://dx.doi.org/10.1038/sj.bjc.6603010
   PubMed Web of Science ®Google Scholar
• Zhou Q, McCracken MA, Strobl JS. Control of mammary tumor cell growth in vitro by novel cell differentiation and apoptosis agents. Breast Cancer Res Treat 2002; 75:107-17; PMID:12243503; http://dx.doi.org/10.1023/A:1019698807564
   PubMed Web of Science ®Google Scholar
• Boya P, Gonzalez-Polo RA, Poncet D, Andreau K, Vieira HL, Roumier T, Perfettini JL, Kroemer G. Mitochondrial membrane permeabilization is a critical step of lysosome-initiated apoptosis induced by hydroxychloroquine. Oncogene 2003; 22:3927-36; PMID:12813466; http://dx.doi.org/10.1038/sj.onc.1206622
   PubMed Web of Science ®Google Scholar
• Amaravadi RK, Yu D, Lum JJ, Bui T, Christophorou MA, Evan GI, Thomas-Tikhonenko A, Thompson CB. Autophagy inhibition enhances therapy-induced apoptosis in a Myc-induced model of lymphoma. J Clin Invest 2007; 117:326-36; PMID:17235397; http://dx.doi.org/10.1172/JCI28833
   PubMed Web of Science ®Google Scholar
• Peters S, Reinthal E, Blitgen-Heinecke P, Bartz-Schmidt KU, Schraermeyer U. Inhibition of lysosomal degradation in retinal pigment epithelium cells induces exocytosis of phagocytic residual material at the basolateral plasma membrane. Ophthalmic Res 2006; 38:83-8; PMID:16352920; http://dx.doi.org/10.1159/000090268
   PubMed Web of Science ®Google Scholar
• Gan B, Peng X, Nagy T, Alcaraz A, Gu H, Guan JL. Role of FIP200 in cardiac and liver development and its regulation of TNFalpha and TSC-mTOR signaling pathways. J Cell Biol 2006; 175:121-33; PMID:17015619; http://dx.doi.org/10.1083/jcb.200604129
   PubMed Web of Science ®Google Scholar
• Kumar AR, Hudson WA, Chen W, Nishiuchi R, Yao Q, Kersey JH. Hoxa9 influences the phenotype but not the incidence of Mll-AF9 fusion gene leukemia. Blood 2004; 103:1823-8; PMID:14615372; http://dx.doi.org/10.1182/blood-2003-07-2582
   PubMed Web of Science ®Google Scholar
• Goyama S, Schibler J, Cunningham L, Zhang Y, Rao Y, Nishimoto N, Nakagawa M, Olsson A, Wunderlich M, Link KA, et al. Transcription factor RUNX1 promotes survival of acute myeloid leukemia cells. J Clin Invest 2013; 123:3876-88; PMID:23979164; http://dx.doi.org/10.1172/JCI68557
   PubMed Web of Science ®Google Scholar
• Krejci O, Wunderlich M, Geiger H, Chou FS, Schleimer D, Jansen M, Andreassen PR, Mulloy JC. p53 signaling in response to increased DNA damage sensitizes AML1-ETO cells to stress-induced death. Blood 2008; 111:2190-9; PMID:17975013; http://dx.doi.org/10.1182/blood-2007-06-093682
   PubMed Web of Science ®Google Scholar
• Wei J, Wunderlich M, Fox C, Alvarez S, Cigudosa JC, Wilhelm JS, Zheng Y, Cancelas JA, Gu Y, Jansen M, et al. Microenvironment determines lineage fate in a human model of MLL-AF9 leukemia. Cancer Cell 2008; 13:483-95; PMID:18538732; http://dx.doi.org/10.1016/j.ccr.2008.04.020
   PubMed Web of Science ®Google Scholar
• Roychoudhury J, Clark JP, Gracia-Maldonado G, Unnisa Z, Wunderlich M, Link KA, Dasgupta N, Aronow B, Huang G, Mulloy JC, et al. MEIS1 regulates an HLF-oxidative stress axis in MLL-fusion gene leukemia. Blood 2015; 125:2544-52; PMID:25740828; http://dx.doi.org/10.1182/blood-2014-09-599258
   PubMed Web of Science ®Google Scholar