Autophagy is a survival mechanism of acute myelogenous leukemia precursors during dual mTORC2/mTORC1 targeting

Clinical Cancer Research

Volumn 20, Issue 9, 2014, Pages 2400-2409

  Altman, Jessica K ^a,b   Szilard, Amy ^a   Goussetis, Dennis J ^a,b   Sassano, Antonella ^a,b   Colamonici, Marco ^a   Gounaris, Elias ^a   Frankfurt, Olga ^a   Giles, Francis J ^a   Eklund, Elizabeth A ^a,b   Beauchamp, Elspeth M ^a,b   Platanias, Leonidas C ^a,b  

^a NORTHWESTERN UNIVERSITY   (United States)

^b JESSE BROWN VA MEDICAL CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

4 (4 AMINO 5 (7 METHOXY 1H INDOL 2 YL)IMIDAZO[5,1 F][1,2,4]TRIAZIN 7 YL)CYCLOHEXANECARBOXYLIC ACID; AZD 2014; CHLOROQUINE; MAMMALIAN TARGET OF RAPAMYCIN COMPLEX 1; MAMMALIAN TARGET OF RAPAMYCIN COMPLEX 2; METHYLCELLULOSE; PROTEIN P62; MECHANISTIC TARGET OF RAPAMYCIN COMPLEX 1; MULTIPROTEIN COMPLEX; PROTEIN KINASE INHIBITOR; TARGET OF RAPAMYCIN KINASE; TOR COMPLEX 2;

ACUTE GRANULOCYTIC LEUKEMIA; ANTINEOPLASTIC ACTIVITY; APOPTOSIS; ARTICLE; AUTOPHAGY; CANCER COMBINATION CHEMOTHERAPY; CANCER RESISTANCE; CANCER STEM CELL; CELL SURVIVAL; CELL VIABILITY; CLONOGENIC ASSAY; CONTROLLED STUDY; DRUG POTENTIATION; DRUG TARGETING; HUMAN; HUMAN CELL; LEUKEMIA CELL; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; REGULATORY MECHANISM; ACUTE MYELOBLASTIC LEUKEMIA; ANTAGONISTS AND INHIBITORS; DRUG EFFECTS; METABOLISM; TUMOR CELL LINE; ULTRASTRUCTURE;

AUTOPHAGY; CELL LINE, TUMOR; CELL SURVIVAL; HUMANS; LEUKEMIA, MYELOID, ACUTE; MULTIPROTEIN COMPLEXES; NEOPLASTIC STEM CELLS; PROTEIN KINASE INHIBITORS; TOR SERINE-THREONINE KINASES;

EID: 84899724396     PISSN: 10780432     EISSN: 15573265     Source Type: Journal    
DOI: 10.1158/1078-0432.CCR-13-3218     Document Type: Article

References (56)

1. Laplante M, Sabatini DM. mTOR signaling in growth control and disease. Cell 2012;149:274-293.
2. 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.
3. Beauchamp EM, Platanias LC. The evolution of the TOR pathway and its role in cancer. Oncogene 2013;32:3923-32.
4. Dancey J. mTOR signaling and drug development in cancer. Nat Rev Clin Oncol 2010;7:209-19.
5. Khokhar NZ, Altman JK, Platanias LC. Emerging roles for mammalian target of rapamycin inhibitors in the treatment of solid tumors and hematological malignancies. Curr Opin Oncol 2011;23:578-86.
6. Johnson SC, Rabinovitch PS, Kaeberlein M. mTOR is a key modulator of ageing and age-related disease. Nature 2013;493:338-45.
7. Lamming DW, Ye L, Sabatini DM, Baur JA. Rapalogs and mTOR inhibitors as anti-aging therapeutics. J Clin Invest 2013;123:980-9.
8. Benjamin D, Colombi M, Moroni C, Hall MN. Rapamycin passes the torch: a new generation of mTOR inhibitors. Nat Rev Drug Discov 2011;10:868-80.
9. Nelson V, Altman JK, Platanias LC. Next generation of mammalian target of rapamycin inhibitors for the treatment of cancer. Exp Opin Invest Drugs 2013;22:715-22.
10. Dohner H, Estey EH, Amadori S, Appelbaum FR, Buchner T, Burneett AK, et al. Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet. Blood 2010;115:453-74.
11. Walter RB, Appelbaum FR, Tallman MS, Weiss NS, Larson RA, Estey EH. Shortcomings in the clinical evaluation of new drugs: acute myeloid leukemia as paradigm. Blood 2010;116:2420-8.
12. Estey EH. Acute myeloid leukemia: 2013 update on risk-stratification and management. Am J Hematol 2013;88:318-27.
13. Altman JK, Platanias LC. Acute myeloid leukemia: potential for new therapeutic approaches targeting mRNA translation pathways. Int J Hematol Oncol 2013;2:243-50.
14. Min YH, Eom JI, Cheong JW, Maeng HO, Kim JY, Jeung HK, et al. Constitutive phosphorylation of Akt/PKB protein in acute myeloid leukemia: its significance as a prognostic variable. Leukemia 2003; 17:995-7.
15. Recher C, Dos Santos C, Demur C, Payrastre B. mTOR, a new therapeutic target in acute myeloid leukemia. Cell Cycle 2005;4:1540-9.
16. Altman JK, Sassano A, Platanias LC. TargetingmTORfor the treatment of AML. New agents and new directions. Oncotarget 2011;2:510-7.
17. Chen W, Drakos E, Grammatikakis I, Schlette EJ, Li J, Leventaki V, et al. mTOR signaling is activated by FLT3 kinase and promotes survival of FLT3-mutated acute myeloid leukemia cells. Mol Cancer 2010;9:292.
18. Recher C, Beyne-Rauzy O, Demur C, Chicanne G, Dos Santos C, Mas VM, et al. Antileukemic activity of rapamycin in acute myeloid leukemia. Blood 2005;105:2527-34.
19. Calabro A, Tai J, Allen SL, Budman DR. In-vitro synergism of m-TOR inhibitors, statins, and classical chemotherapy: potential implications in acute leukemia. Anticancer Drugs 2008;19:705-12.
20. Altman JK, Yoon P, Katsoulidis E, Kroczynska B, Sassano A, Redig AJ, et al. Regulatory effects of mammalian target of rapamycin-mediated signals in the generation of arsenic trioxide responses. J Biol Chem 2008;283:1992-2001.
21. Nishioka C, Ikezoe T, Yang J, Gery S, Koeffler HP, Yokoyama A. Inhibition of mammalian target of rapamycin signaling potentiates the effects of all-trans retinoic acid to induce growth arrest and differentiation of human acute myelogenous leukemia cells. Int J Cancer 2009;125:1710-20.
22. Perl AE, Kasner MT, Tsai DE, Vogl DT, Loren AW, Schuster SJ, et al. A phase I study of the mammalian target of rapamycin inhibitor sirolimus andMECchemotherapy in relapsed and refractory acute myelogenous leukemia. Clin Cancer Res 2009;15:6732-9.
23. Amadori S, Stasi R, Martelli AM, Venditti A, Meloni G, Pane F, et al. 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). Br J Haematol 2012;156:205-12.
24. Altman JK, Sassano A, Kaur S, Glaser H, Kroczynska B, Redig AJ, et al. Dual mTORC2/mTORC1 targeting results in potent suppressive effects on acute myeloid leukemia (AML) progenitors. Clin Cancer Res 2011;17:4378-88.
25. Willems L, Chapuis N, Puissant A, Maciel TT, Green AS, Jacque N, et al. The dual mTORC1 and mTORC2 inhibitor AZD8055 has anti-tumor activity in acute myeloid leukemia. Leukemia 2012;26:1195-1202.
26. Zeng Z, Shi YX, Tsao T, Qiu Y, Kornblau SM, Baggerly KA, et al. Targeting of mTORC1/2 by the mTOR kinase inhibitor PP242 induces apoptosis in AML cells under conditions mimicking the bone marrow microenvironment. Blood 2012;120:2679-89.
27. Kaur S, Sassano A, Dolniak B, Joshi S, Majchrzak-Kita B, Baker DP, et al. Role of the Akt pathway in mRNA translation of interferonstimulated genes. Proc Natl Acad Sci U S A 2008;105:4808-13.
28. Kaur S, Sassano A, Majchrzak-Kita B, Baker DP, Su B, Fish EN, et al. Regulatory effects ofmTORC2 complexes in type I IFN signaling and in the generation of IFN responses. Proc Natl Acad Sci USA 2012; 109:7723-8.
29. Carayol N, Katsoulidis E, Sassano A, Altman JK, Druker BJ, Platanias LC. Suppression of programmed cell death 4 (PDCD4) protein expression by BCR-ABL-regulated engagement of the mTOR/p70 S6 kinase pathway. J Biol Chem 2008;283:8601-10.
30. Giafis N, Katsoulidis E, Sassano A, Tallman MS, Higgins LS, Nebreda AR, et al. Role of the p38 mitogen-activated protein kinase pathway in the generation of arsenic trioxide-dependent cellular responses. Cancer Res 2006;66:6763-71.
31. Vakana E, Altman JK, Glaser H, Donato NJ, Platanias LC. Antileukemic effects of AMPK activators on BCR-ABL-expressing cells. Blood 2011;118:6399-6402.
32. Altman JK, Szilard A, Konicek BW, Iversen PW, Kroczynska B, Glaser H, et al. Inhibition of Mnk kinase activity by cercosporamide and suppressive effects on acute myeloid leukemia precursors. Blood 2013;121:3675-81.
33. Goussetis DJ, Gounaris E,WuEJ, Vakana E, Sharma B, Bogyo M, et al. Autophagic degradation of the BCR-ABL oncoprotein and generation of antileukemic responses by arsenic trioxide. Blood 2012;120: 3555-62.
34. Goussetis DJ, Altman JK, Glaser H, McNeer JL, Tallman MS, Platanias LC. Autophagy is a critical mechanism for the induction of the antileukemic effects of arsenic trioxide. J Biol Chem 2010; 285:29989-97.
35. Yla-Anttila P, Vihinen H, Jokitalo E, Eskelinen EL. Monitoring autophagy by electron microscopy in mammalian cells. Methods Enzymol 2009;452:143-64.
36. Tan AS, Berridge MV. Superoxide produced by activated neutrophils efficiently reduces the tetrazolium salt, WST-1 to produce a soluble formazan: a simple colorimetric assay for measuring respiratory burst activation and for screening anti-inflammatory agents. J Immunol Methods 2000;238:59-68.
37. Mizushima N, Yoshimori T, Levine B. Methods in mammalian autophagy research. Cell 2010;140:313-26.
38. Amaravadi RK, Yu D, Lum JJ, Bui T, Christophorou MA, Evan GI, et al. Autophagy inhibition enhances therapy-induced apoptosis in a Mycinduced model of lymphoma. J Clin Invest 2007;117:326-36.
39. Pike KG, Malagu K, Hummersone MG, Menear KA, Duggan HM, Gomez S, et al. Optimization of potent and selective dual mTORC1 and mTORC2 inhibitors: the discovery of AZD8055 and AZD2014. Bioorg Med Chem Lett 2013;23:1212-6.
40. Kim J, Kundu M, Viollet B, Guan KL. AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1. Nat Cell Biol 2013;13:132-41.
41. Xu Q, Simpson S, Scialla TJ, Bagg A, Carroll M. Survival of acute myeloid leukemia required PI3 kinase activation. Blood 2003;102: 972-80.
42. Grandage VL, Gale RE, Linch DC, Khwaja A. PI3-kinase/Akt is constitutively active in primary acute myeloid leukaemia cells and regulates survival and chemoresistance via NF-kB, Mapkinase and p53 pathways. Leukemia 2005;19:586-94.
43. Altman JK, Platanias LC. Exploiting the mammalian target of rapamycin pathway in hematologic malignancies. Curr Opin Hematol 2008; 15:88-94.
44. Xu Q, Thompson JE, Carroll M. mTOR regulates cell survival after etoposide treatment in primary AML cells. Blood 2005;106:4261-8.
45. Park S, Chapuis N, Saint Marcoux F, Recher C, Prebet T, Chevallier P, et al. A phase Ib GOELAMS study of the mTOR inhibitor RAD001 in association with chemotherapy for AML patients in first relapse. Leukemia 2013;27:1479-86.
46. Carayol N, Vakana E, Sassano A, Kaur S, Goussetis DJ, Glaser H, et al. Critical roles for mTORC2-and rapamycin-insensitive mTORC1-complexes in growth and survival of BCR-ABL-expressing leukemic cells. Proc Natl Acad Sci USA 2010;107:12469-74.
47. Meng H, Jin Y, Liu H, You L, Yang C, Yang X, et al. SNS-032 inhibits mTORC1/ mTORC2 activity in acute myeloid leukemia cells and has synergistic activity with perifosine against Akt. J Hematol Oncol 2013; 6:18.
48. Bogani C, Bartalucci N, Martinelli S, Tozzi L, Guglielmelli P, Bosi A, et al. mTOR inhibitors alone and in combination with JAK2 inhibitors effectively inhibit cells of myeloproliferative neoplasms. PLoS ONE 2013;8: e54826.
49. Nelson V, Altman JK, Platanias LC. Next generation of mammalian target of rapamycin inhibitors for the treatment of cancer. Expert Opin Invest Drugs 2013;22:715-22.
50. Gupta M, Hendrickson AE, Yun SS, Han JJ, Schneider PA, Koh BD, et al. Dual mTORC1/mTORC2 inhibition diminishes Akt activation and induces Puma-dependent apoptosis in lymphoid malignancies. Blood 2012;119:476-87.
51. Maiso P, Liu Y, Morgan B, Azab AK, Ren P, Martin MB, et al. Defining the role of TORC1/2 in multiple myeloma. Blood 2011; 118:6860-70.
52. Kampa-Schittenhelm KM, Heinrich MC, Akmut F, Rasp KH, Illing B, Dohner H, et al. Cell cycle-dependent activity of the novel dual PI3KMTORC1/ 2 inhibitor NVP-BGT226 in acute leukemia. Mol Cancer 2013;12:46.
53. Rubinsztein DC, Codogno P, Levine B. Autophagy modulation as a potential therapeutic target for diverse diseases. Nat Rev Drug Discov 2012;11:709-30.
54. Isakson P, Bjøras M, Bøe SO, Simonsen A. Autophagy contributes to therapy-induced degradation of the PML/RARA oncoprotein. Blood 2010;116:2324-31.
55. Torgersen ML, Engedal N, Bøe 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.
56. Liu LL, Long ZJ, Wang LX, Zheng FM, Fang ZG, Yan M, et al. Inhibition of mTOR pathway sensitizes acute myeloid leukemia cells to Aurora inhibitors by suppression of glycolytic metabolism. Mol Cancer Res 2013;11:1326-36.