Inhibition of PI3K/mTOR overcomes nilotinib resistance in BCR-ABL1 positive leukemia cells through translational down-regulation of MDM2

PLoS ONE

Volumn 8, Issue 12, 2013, Pages

  Ding, Jie ^a   Romani, Julia ^a   Zaborski, Margarete ^a   MacLeod, Roderick A F ^a   Nagel, Stefan ^a   Drexler, Hans G ^a   Quentmeier, Hilmar ^a  

^a LEIBNIZ INSTITUTE DSMZ GERMAN COLLECTION OF MICROORGANISMS AND CELL CULTURES   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

BCR ABL1 PROTEIN; CRK LIKE PROTEIN; DACTOLISIB; EVEROLIMUS; GRB ASSOCIATED BINDER 2 PROTEIN; HYBRID PROTEIN; IMATINIB; LIPOCORTIN 5; MAMMALIAN TARGET OF RAPAMYCIN; NILOTINIB; PHOSPHATIDYLINOSITOL 3 KINASE; PROPIDIUM IODIDE; PROTEIN MDM2; PROTEIN TYROSINE KINASE INHIBITOR; SCAFFOLD PROTEIN; UNCLASSIFIED DRUG;

APOPTOSIS; ARTICLE; BCR ABL1 POSITIVE LEUKEMIA CELL; CANCER RESISTANCE; CELL LINE; DOWN REGULATION; DRUG POTENTIATION; DRUG RESPONSE; DRUG SENSITIZATION; DRUG TARGETING; ENZYME INACTIVATION; ENZYME INHIBITION; HUMAN; HUMAN CELL; JURL-MK2 CELL; LEUKEMIA CELL; PHILADELPHIA CHROMOSOME POSITIVE CELL; PROPIDIUM IODIDE ASSAY; PROTEIN DEPHOSPHORYLATION; RNA TRANSLATION; SUP-B15 CELL;

CELL LINE, TUMOR; DOWN-REGULATION; DRUG RESISTANCE, NEOPLASM; FUSION PROTEINS, BCR-ABL; GENE EXPRESSION REGULATION, LEUKEMIC; HUMANS; IMIDAZOLES; LEUKEMIA; PHOSPHATIDYLINOSITOL 3-KINASES; PROTEIN KINASE INHIBITORS; PROTO-ONCOGENE PROTEINS C-MDM2; PYRIMIDINES; QUINOLINES; TOR SERINE-THREONINE KINASES;

EID: 84892568018     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0083510     Document Type: Article

References (49)

1. Manley PW, Breitenstein W, Brüggen J, Cowan-Jacob SW, Furet P et al. (2004) Urea-derivatives of STI571 as inhibitors of Bcr-Abl and PDGFR kinases. Bioorg Med Chem Lett 14: 5793-5797. doi:10.1016/j.bmcl.2004.09.042. PubMed: 15501042.
2. Weisberg E, Manley PW, Breitenstein W, Brüggen J, Cowan-Jacob SW et al. (2005) Characterization of AMN107, a selective inhibitor of native and mutant BCR-ABL. Cancer Cell 7: 129-141. doi:10.1016/j.ccr.2005.01.007. PubMed: 15710326.
3. Giles FJ, le Coutre PD, Pinilla-Ibarz J, Larson RA, Gattermann N et al. (2013) Nilotinib in imatinib-resistant or imatinib-intolerant patients with chronic myeloid leukemia in chronic phase: 48-month follow-up results of a phase II study. Leukemia 27: 107-112. doi:10.1038/leu.2012.181. PubMed: 22763385.
4. Parker WT, Yeoman AL, Jamison BA, Yeung DT, Scott HS et al. (2013) BCR-ABL1 kinase domain mutations may persist at very low levels for many years and lead to subsequent TKI resistance. Br J Cancer, 109: 1593-8. doi:10.1038/bjc.2013.318. [Epub ahead of print] PubMed: 23799845.
5. Griffin JD, Guerin A, Chen L, Macalalad AR, Luo J et al. (2013) Comparing nilotinib with dasatinib as second-line therapies in patients with chronic myelogenous leukemia resistant or intolerant to imatinib - a retrospective chart review analysis. Curr Med Res Opin 29: 623-631. PubMed: 23517347.
6. Jabbour E, Cortes J, Kantarjian H (2010) Nilotinib for the treatment of chronic myeloid leukemia: An evidence-based review. Core Evid 4: 207-213. PubMed: 20694077.
7. Manley PW, Cowan-Jacob SW, Mestan J (2005) Advances in the structural biology, design and clinical development of Bcr-Abl kinase inhibitors for the treatment of chronic myeloid leukaemia. Biochim Biophys Acta 1754: 3-13. doi:10.1016/j.bbapap.2005.07.040. PubMed: 16172030.
8. Manley PW, Stiefl N, Cowan-Jacob SW, Kaufman S, Mestan J et al. (2010) Structural resemblances and comparisons of the relative pharmacological properties of imatinib and nilotinib. Bioorg Med Chem 18: 6977-6986. doi:10.1016/j.bmc.2010.08.026. PubMed: 20817538.
9. Mahon FX, Hayette S, Lagarde V, Belloc F, Turcq B et al. (2008) Evidence that resistance to nilotinib may be due to BCR-ABL, Pgp, or Src kinase overexpression. Cancer Res 68: 9809-9816. doi: 10.1158/0008-5472.CAN-08-1008. PubMed: 19047160.
10. Camgoz A, Gencer EB, Ural AU, Baran Y (2013) Mechanisms responsible for nilotinib resistance in human chronic myeloid leukemia cells and reversal of resistance. Leuk Lymphoma 54: 1279-1287. doi: 10.3109/10428194.2012.737919. PubMed: 23098068.
11. Quentmeier H, Eberth S, Romani J, Zaborski M, Drexler HG (2011) BCR-ABL1-independent PI3Kinase activation causing imatinibresistance. J Hematol Oncol 4: 6. doi:10.1186/1756-8722-4-6. PubMed: 21299849.
12. Wöhrle FU, Halbach S, Aumann K, Schwemmers S, Braun S et al. (2013) Gab2 signaling in chronic myeloid leukemia cells confers resistance to multiple Bcr-Abl inhibitors. Leukemia 27: 118-129. doi: 10.1038/leu.2012.222. PubMed: 22858987.
13. Martelli AM, Chiarini F, Evangelisti C, Cappellini A, Buontempo F et al. (2012) Two hits are better than one: targeting both phosphatidylinositol 3-kinase and mammalian target of rapamycin as a therapeutic strategy for acute leukemia treatment. Oncotarget 3: 371-394. PubMed: 22564882.
14. Hara K, Maruki Y, Long X, Yoshino K, Oshiro N et al. (2002) Raptor, a binding partner of target of rapamycin (TOR), mediates TOR action. Cell 110: 177-189. doi:10.1016/S0092-8674(02)00833-4. PubMed: 12150926.
15. Guertin DA, Sabatini DM (2007) Defining the role of mTOR in cancer. Cancer Cell 12: 9-22. doi:10.1016/j.ccr.2007.05.008. PubMed: 17613433.
16. Engelman JA (2009) Targeting PI3K signalling in cancer: opportunities, challenges and limitations. Nat Rev Cancer 9: 550-562. doi:10.1038/nrc2664. PubMed: 19629070.
17. Faivre S, Kroemer G, Raymond E (2006) Current development of mTOR inhibitors as anticancer agents. Nat Rev Drug Discov 5: 671-688. doi:10.1038/nrd2062. PubMed: 16883305.
18. Hennessy BT, Smith DL, Ram PT, Lu Y, Mills GB (2005) Exploiting the PI3K/AKT pathway for cancer drug discovery. Nat Rev Drug Discov 4: 988-1004. doi:10.1038/nrd1902. PubMed: 16341064.
19. Feng J, Tamaskovic R, Yang Z, Brazil DP, Merlo A (2004) Stabilization of Mdm2 via decreased ubiquitination is mediated by protein kinase B/Akt-dependent phosphorylation. J Biol Chem 279: 35510-35517. PubMed: 15169778.
20. Tabe Y, Sebasigari D, Jin L, Rudelius M, Davies-Hill T et al. (2009) MDM2 antagonist nutlin?3 displays antiproliferative and proapoptotic activity in mantle cell lymphoma. Clin Cancer Res 15: 933-942. doi: 10.1158/1078-0432.CCR- 08-0399. PubMed: 19188164.
21. Gu L, Zhu N, Findley HW, Zhou M (2008) MDM2 antagonist nutlin-3 is a potent inducer of apoptosis in pediatric acute lymphoblastic leukemia cells with wild-type p53 and overexpression of MDM2. Leukemia 22: 730-739. doi:10.1038/leu.2008.11. PubMed: 18273046.
22. Logan IR, McNeill HV, Cook S, Lu X, Lunec J et al. (2007) Analysis of the MDM2 antagonist nutlin-3 in human prostate cancer cells. Prostate 67: 900-906. doi:10.1002/pros.20568. PubMed: 17440969.
23. VanderBorght A, Valckx A, Van Dun J, Grand-Perret T, De Schepper S et al. (2006) Effect of an hdm-2 antagonist peptide inhibitor on cell cycle progression in p53-deficient H1299 human lung carcinoma cells. Oncogene 25: 6672-6677. doi:10.1038/sj.onc.1209667. PubMed: 16732328.
24. Secchiero P, Barbarotto E, Tiribelli M, Zerbinati C, di Iasio MG et al. (2006) Functional integrity of the p53-mediated apoptotic pathway induced by the nongenotoxic agent nutlin-3 in B-cell chronic lymphocytic leukemia (B-CLL). Blood 107: 4122-4129. doi:10.1182/blood-2005-11-4465. PubMed: 16439677.
25. Coll-Mulet L, Iglesias-Serret D, Santidrián AF, Cosialls AM, de Frias M et al. (2006) MDM2 antagonists activate p53 and synergize with genotoxic drugs in B-cell chronic lymphocytic leukemia cells. Blood 107: 4109-4114. doi:10.1182/blood-2005-08-3273. PubMed: 16439685.
26. Manfredi JJ (2010) The Mdm2-p53 relationship evolves: Mdm2 swings both ways as an oncogene and a tumor suppressor. Genes Dev 24: 1580-1589. doi:10.1101/gad.1941710. PubMed: 20679392.
27. Lundgren K, Montes de Oca Luna R, McNeill YB, Emerick EP, Spencer B et al. (1997) Targeted expression of MDM2 uncouples S phase from mitosis and inhibits mammary gland development independent of p53. Genes Dev 11: 714-725. doi:10.1101/gad.11.6.714. PubMed: 9087426.
28. Gu L, Zhu N, Zhang H, Durden DL, Feng Y et al. (2009) Regulation of XIAP translation and induction by MDM2 following irradiation. Cancer Cell 15: 363-375. doi:10.1016/j.ccr.2009.03.002. PubMed: 19411066.
29. Maira SM, Stauffer F, Brueggen J, Furet P, Schnell C et al. (2008) Identification and characterization of NVP-BEZ235, a new orally available dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor with potent in vivo antitumor activity. Mol Cancer Ther 7: 1851-1863. doi:10.1158/1535-7163.MCT-08-0017. PubMed: 18606717.
30. Marone R, Erhart D, Mertz AC, Bohnacker T, Schnell C et al. (2009) Targeting melanoma with dual phosphoinositide 3-kinase/mammalian target of rapamycin inhibitors. Mol Cancer Res 7: 601-613. doi: 10.1158/1541-7786.MCR-08- 0366. PubMed: 19372588.
31. Manara MC, Nicoletti G, Zambelli D, Ventura S, Guerzoni C et al. (2010) NVP-BEZ235 as a new therapeutic option for sarcomas. Clin Cancer Res 16: 530-540. doi:10.1158/1078-0432.CCR-09-0816. PubMed: 20068094.
32. Chapuis N, Tamburini J, Green AS, Vignon C, Bardet V et al. (2010) Dual inhibition of PI3K and mTORC1/2 signaling by NVP-BEZ235 as a new therapeutic strategy for acute myeloid leukemia. Clin Cancer Res 16: 5424-5435. doi:10.1158/1078-0432.CCR-10-1102. PubMed: 20884625.
33. Santiskulvong C, Konecny GE, Fekete M, Chen KY, Karam A et al. (2011) Dual targeting of phosphoinositide 3-kinase and mammalian target of rapamycin using NVP-BEZ235 as a novel therapeutic approach in human ovarian carcinoma. Clin Cancer Res 17: 2373-2384. doi:10.1158/1078-0432.CCR-10-2289. PubMed: 21372221.
34. Drexler HG (2010) Guide to Leukemia-Lymphoma Cell Lines. 2nd Edition. Braunschweig.
35. Quentmeier H, Schneider B, Röhrs S, Romani J, Zaborski M et al. (2009) SET-NUP214 fusion in acute myeloid leukemia- and T-cell acute lymphoblastic leukemia-derived cell lines. J Hematol Oncol 2: 3. doi: 10.1186/1756-8722-2-3. PubMed: 19166587.
36. Lapenna S, Giordano A (2009) Cell cycle kinases as therapeutic targets for cancer. Nat Rev Drug Discov 8: 547-566. doi:10.1038/nrd2907. PubMed: 19568282.
37. Chiarini F, Grimaldi C, Ricci F, Tazzari PL, Evangelisti C et al. (2010) Activity of the novel dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor NVP-BEZ235 against T-cell acute lymphoblastic leukemia. Cancer Res 70: 8097-8107. doi: 10.1158/0008-5472.CAN-10-1814. PubMed: 20876803.
38. Schult C, Dahlhaus M, Glass A, Fischer K, Lange S et al. (2012) The dual kinase inhibitor NVP-BEZ235 in combination with cytotoxic drugs exerts anti-proliferative activity towards acute lymphoblastic leukemia cells. Anticancer Res 32: 463-474. PubMed: 22287733.
39. Mamane Y, Petroulakis E, LeBacquer O, Sonenberg N (2006) mTOR, translation initiation and cancer. Oncogene 25: 6416-6422. doi: 10.1038/sj.onc.1209888. PubMed: 17041626.
40. Gingras AC, Raught B, Sonenberg N (1999) eIF4 initiation factors: effectors of mRNA recruitment to ribosomes and regulators of translation. Annu Rev Biochem 68: 913-963. doi:10.1146/annurev.biochem.68.1.913. PubMed: 10872469.
41. Deininger MW, Goldman JM, Lydon N, Melo JV (1997) The tyrosine kinase inhibitor CGP57148B selectively inhibits the growth of BCR-ABL-positive cells. Blood 90: 3691-3698. PubMed: 9345054.
42. Adams SJ, Aydin IT, Celebi JT (2012) GAB2 - a scaffolding protein in cancer. Mol Cancer Res 10: 1265-1270. doi: 10.1158/1541-7786.MCR-12-0352. PubMed: 22871571.
43. Aumann K, Lassmann S, Schöpflin A, May AM, Wöhrle FU et al. (2011) The immunohistochemical staining pattern of Gab2 correlates with distinct stages of chronic myeloid leukemia. Hum Pathol 42: 719-726. PubMed: 21292300.
44. Scherr M, Chaturvedi A, Battmer K, Dallmann I, Schultheis B et al. (2006) Enhanced sensitivity to inhibition of SHP2, STAT5, and Gab2 expression in chronic myeloid leukemia (CML). Blood 107: 3279-3287. doi:10.1182/blood-2005-08- 3087. PubMed: 16278304.
45. Sattler M, Mohi MG, Pride YB, Quinnan LR, Malouf NA et al. (2002) Critical role for Gab2 in transformation by BCR/ABL. Cancer Cell 1: 479-492. doi:10.1016/S1535-6108(02)00074-0. PubMed: 12124177.
46. Zhou M, Yeager AM, Smith SD, Findley HW (1995) Overexpression of the MDM2 gene by childhood acute lymphoblastic leukemia cells expressing the wild-type p53 gene. Blood 85: 1608-1614. PubMed: 7888679.
47. Itahana K, Mao H, Jin A, Itahana Y, Clegg HV et al. (2007) Targeted inactivation of Mdm2 RING finger E3 ubiquitin ligase activity in the mouse reveals mechanistic insights into p53 regulation. Cancer Cell 12: 355-366. doi:10.1016/j.ccr.2007.09.007. PubMed: 17936560.
48. Coleman ML, Marshall CJ, Olson MF (2004) RAS and RHO GTPases in G1-phase cell-cycle regulation. Nat Rev Mol Cell Biol 5: 355-366. doi:10.1038/nrm1365. PubMed: 15122349.
49. Polak R, Buitenhuis M (2012) The PI3K/PKB signaling module as key regulator of hematopoiesis: implications for therapeutic strategies in leukemia. Blood 119: 911-923. doi:10.1182/blood-2011-07-366203. PubMed: 22065598.