Preclinical and clinical efficacy of XPO1/CRM1 inhibition by the karyopherin inhibitor KPT-330 in Ph+ leukemias

Blood

Volumn 122, Issue 17, 2013, Pages 3034-3044

  Walker, Christopher J ^a   Oaks, Joshua J ^a   Santhanam, Ramasamy ^a   Neviani, Paolo ^a,b   Harb, Jason G ^a   Ferenchak, Gregory ^a   Ellis, Justin J ^a   Landesman, Yosef ^c   Eisfeld, Ann Kathrin ^a   Gabrail, Nash Y ^d   Smith, Carrie L ^d   Caligiuri, Michael A ^a,b   Hokland, Peter ^e   Roy, Denis Claude ^f   Reid, Alistair ^g   Milojkovic, Dragana ^g   Goldman, John M ^g   Apperley, Jane ^g   Garzon, Ramiro ^a,b   Marcucci, Guido ^a,b   Shacham, Sharon ^c   Kauffman, Michael G ^c   Perrotti, Danilo ^a,b,g,h   more..

^a Department Molecular Virology Immunology and Medical Genetics ^*  (United States)

^b OHIO STATE UNIVERSITY   (United States)

^c Karyopharm Therapeutics   (United States)

^d Gabrail Cancer Center   (United States)

^e AARHUS UNIVERSITY HOSPITAL   (Denmark)

^f UNIVERSITÉ DE MONTRÉAL   (Canada)

^g HAMMERSMITH HOSPITAL   (United Kingdom)

^h UNIVERSITY OF MARYLAND GREENEBAUM CANCER CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

1,4 DIAMINO 1,4 BIS(2 AMINOPHENYLTHIO) 2,3 DICYANOBUTADIENE; 2 MORPHOLINO 8 PHENYLCHROMONE; 4 AMINO 7 TERT BUTYL 5 (4 CHLOROPHENYL)PYRAZOLO[3,4 D]PYRIMIDINE; AZACITIDINE; BCR ABL PROTEIN; CD34 ANTIGEN; EXPORTIN 1; FEDRATINIB; HETEROGENEOUS NUCLEAR RIBONUCLEOPROTEIN; HETEROGENEOUS NUCLEAR RIBONUCLEOPROTEIN A1; HOMOHARRINGTONINE; I KAPPA B; IMATINIB; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INTERFERON; INTERLEUKIN 3; JANUS KINASE 2; KARYOPHERIN; KPT 185; KPT 207; LACTATE DEHYDROGENASE; MIDOSTAURIN; MITOGEN ACTIVATED PROTEIN KINASE; PHOSPHATIDYLINOSITOL 3 KINASE; PHOSPHOPROTEIN PHOSPHATASE 2A; PROTEIN P53; SELINEXOR; STAT5 PROTEIN; TRANSCRIPTION FACTOR FKHRL1; UNCLASSIFIED DRUG; ANTINEOPLASTIC AGENT; BCR ABL1 FUSION PROTEIN, HUMAN; BCR-ABL1 FUSION PROTEIN, HUMAN; CELL RECEPTOR; CHAPERONE; EXPORTIN 1 PROTEIN; HYDRAZINE DERIVATIVE; KPT 330; KPT-330; PROTEIN KINASE INHIBITOR; RIBONUCLEOPROTEIN; SET PROTEIN, HUMAN; TRANSCRIPTION FACTOR; TRIAZOLE DERIVATIVE;

ACUTE LYMPHOBLASTIC LEUKEMIA; ADULT; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; APOPTOSIS; ARTICLE; BLAST CELL; BLAST CELL CRISIS; BONE PAIN; CANCER RESISTANCE; CANCER SURVIVAL; CASE REPORT; CELL SURVIVAL; CELLULAR DISTRIBUTION; CHRONIC MYELOID LEUKEMIA; COMPASSIONATE USE; CONTROLLED STUDY; DISEASE COURSE; DRUG EFFICACY; ENZYME INHIBITION; GENE OVEREXPRESSION; HUMAN; HUMAN CELL; HUMAN TISSUE; IN VITRO STUDY; LEUKEMIA CELL; LEUKEMOGENESIS; LEUKOCYTE COUNT; MALE; MOUSE; NONHUMAN; NUCLEAR EXPORT; ONCOGENE; PHILADELPHIA CHROMOSOME POSITIVE CELL; PRIORITY JOURNAL; PROTEIN EXPRESSION; RNA BINDING; SPLENOMEGALY; STEM CELL; ANIMAL; CELL PROLIFERATION; DRUG ANTAGONISM; DRUG EFFECT; DRUG SCREENING; GENE EXPRESSION REGULATION; GENETICS; METABOLISM; PATHOLOGY; PHASE 1 CLINICAL TRIAL (TOPIC); PROTEIN TRANSPORT; ANTAGONISTS AND INHIBITORS; DRUG EFFECTS; LEUKEMIA, MYELOGENOUS, CHRONIC, BCR-ABL POSITIVE; PRECURSOR CELL LYMPHOBLASTIC LEUKEMIA-LYMPHOMA;

ADULT; ANIMALS; ANTIGENS, CD34; ANTINEOPLASTIC AGENTS; APOPTOSIS; CELL PROLIFERATION; CLINICAL TRIALS, PHASE I AS TOPIC; DRUG EVALUATION, PRECLINICAL; FUSION PROTEINS, BCR-ABL; GENE EXPRESSION REGULATION, LEUKEMIC; HISTONE CHAPERONES; HUMANS; HYDRAZINES; KARYOPHERINS; LEUKEMIA, MYELOGENOUS, CHRONIC, BCR-ABL POSITIVE; MALE; MICE; PRECURSOR CELL LYMPHOBLASTIC LEUKEMIA-LYMPHOMA; PROTEIN KINASE INHIBITORS; PROTEIN TRANSPORT; RECEPTORS, CYTOPLASMIC AND NUCLEAR; RIBONUCLEOPROTEINS; TRANSCRIPTION FACTORS; TRIAZOLES;

EID: 84888212935     PISSN: 00064971     EISSN: 15280020     Source Type: Journal    
DOI: 10.1182/blood-2013-04-495374     Document Type: Article

References (52)

1. Perrotti D, Jamieson C, Goldman J, Skorski T. Chronic myeloid leukemia: mechanisms of blastic transformation. J Clin Invest. 2010;120(7): 2254-2264.
2. Cortes J, Kantarjian H. How I treat newly diagnosed chronic phase CML. Blood. 2012; 120(7):1390-1397.
3. Hochhaus A, O'Brien SG, Guilhot F, et al; IRIS Investigators. Six-year follow-up of patients receiving imatinib for the first-line treatment of chronic myeloid leukemia. Leukemia. 2009;23(6): 1054-1061.
4. Hehlmann R. How I treat CML blast crisis. Blood. 2012;120(4):737-747.
5. Milojkovic D, Apperley JF, Gerrard G, et al. Responses to second-line tyrosine kinase inhibitors are durable: an intention-to-treat analysis in chronic myeloid leukemia patients. Blood. 2012;119(8):1838-1843.
6. Karvela M, Helgason GV, Holyoake TL. Mechanisms and novel approaches in overriding tyrosine kinase inhibitor resistance in chronic myeloid leukemia. Expert Rev Anticancer Ther. 2012;12(3):381-392.
7. Lee HJ, Thompson JE, Wang ES, Wetzler M. Philadelphia chromosome-positive acute lymphoblastic leukemia: current treatment and future perspectives. Cancer. 2011;117(8): 1583-1594.
8. Cortes JE, Kantarjian H, Shah NP, et al. Ponatinib in refractory Philadelphia chromosome-positive leukemias. N Engl J Med. 2012;367(22): 2075-2088.
9. Eiring AM, Khorashad JS, Morley K, Deininger MW. Advances in the treatment of chronic myeloid leukemia. BMC Med. 2011;9:99.
10. Melo JV, Barnes DJ. Chronic myeloid leukaemia as a model of disease evolution in human cancer. Nat Rev Cancer. 2007;7(6):441-453.
11. Eiring AM, Neviani P, Santhanam R, et al. Identification of novel posttranscriptional targets of the BCR/ABL oncoprotein by ribonomics: requirement of E2F3 for BCR/ABL leukemogenesis. Blood. 2008;111(2):816-828.
12. Baou M, Norton JD, Murphy JJ. AU-rich RNA binding proteins in hematopoiesis and leukemogenesis. Blood. 2011;118(22): 5732-5740.
13. Eiring AM, Harb JG, Neviani P, et al. miR-328 functions as an RNA decoy to modulate hnRNP E2 regulation of mRNA translation in leukemic blasts. Cell. 2010;140(5):652-665.
14. Siddiqui N, Borden KL. mRNA export and cancer. Wiley Interdiscip Rev RNA. 2012;3(1):13-25.
15. Perrotti D, Harb JG. BCR-ABL1 kinase-dependent alteration of mRNA metabolism: potential alternatives for therapeutic intervention. Leuk Lymphoma. 2011;52(Suppl 1):30-44.
16. Xu D, Farmer A, Chook YM. Recognition of nuclear targeting signals by Karyopherin-β proteins. Curr Opin Struct Biol. 2010;20(6): 782-790.
17. Popa I, Harris ME, Donello JE, Hope TJ. CRM1-dependent function of a cis-acting RNA export element. Mol Cell Biol. 2002;22(7):2057-2067.
18. Radu A, Blobel G, Moore MS. Identification of a protein complex that is required for nuclear protein import and mediates docking of import substrate to distinct nucleoporins. Proc Natl Acad Sci USA. 1995;92(5):1769-1773.
19. Fornerod M, Ohno M, Yoshida M, Mattaj IW. CRM1 is an export receptor for leucine-rich nuclear export signals. Cell. 1997;90(6): 1051-1060.
20. Hwang CY, Kim IY, Kwon KS. Cytoplasmic localization and ubiquitination of p21(Cip1) by reactive oxygen species. Biochem Biophys Res Commun. 2007;358(1):219-225.
21. van der Watt PJ, Maske CP, Hendricks DT, et al. The Karyopherin proteins, Crm1 and Karyopherin beta1, are overexpressed in cervical cancer and are critical for cancer cell survival and proliferation. Int J Cancer. 2009;124(8): 1829-1840.
22. Etchin J, Sun Q, Kentsis A, et al. Antileukemic activity of nuclear export inhibitors that spare normal hematopoietic cells. Leukemia. 2013; 27(1):66-74.
23. Kojima K, Kornblau SM, Ruvolo V, et al. Prognostic impact and targeting of CRM1 in acute myeloid leukemia. Blood. 2013;121(20): 4166-4174.
24. Ranganathan P, Yu X, Na C, et al. Preclinical activity of a novel CRM1 inhibitor in acute myeloid leukemia. Blood. 2012;120(9):1765-1773.
25. Lapalombella R, Sun Q, Williams K, et al. Selective inhibitors of nuclear export show that CRM1/XPO1 is a target in chronic lymphocytic leukemia. Blood. 2012;120(23):4621-4634.
26. Zhang K, Wang M, Tamayo AT, et al. Novel selective inhibitors of nuclear export CRM1 antagonists for therapy in mantle cell lymphoma. Exp Hematol. 2013;41(1):67-78, e4.
27. Yao Y, Dong Y, Lin F, et al. The expression of CRM1 is associated with prognosis in human osteosarcoma. Oncol Rep. 2009;21(1):229-235.
28. Inoue H, Kauffman M, Shacham S, et al. CRM1 blockade by selective inhibitors of nuclear export attenuates kidney cancer growth. J Urol. 2013; 189(6):2317-2326.
29. Huang WY, Yue L, Qiu WS, Wang LW, Zhou XH, Sun YJ. Prognostic value of CRM1 in pancreas cancer. Clin Invest Med. 2009;32(6):E315.
30. Noske A, Weichert W, Niesporek S, et al. Expression of the nuclear export protein chromosomal region maintenance/exportin 1/Xpo1 is a prognostic factor in human ovarian cancer. Cancer. 2008;112(8):1733-1743.
31. Turner JG, Dawson J, Sullivan DM. Nuclear export of proteins and drug resistance in cancer. Biochem Pharmacol. 2012;83(8):1021-1032.
32. Etchin J, Sanda T, Mansour MR, et al. KPT-330 inhibitor of CRM1 (XPO1)-mediated nuclear export has selective anti-leukaemic activity in preclinical models of T-cell acute lymphoblastic leukaemia and acute myeloid leukaemia. Br J Haematol. 2013;161(1):117-127.
33. Neviani P, Santhanam R, Trotta R, et al. The tumor suppressor PP2A is functionally inactivated in blast crisis CML through the inhibitory activity of the BCR/ABL-regulated SET protein. Cancer Cell. 2005;8(5):355-368.
34. Neviani P, Santhanam R, Oaks JJ, et al. FTY720, a new alternative for treating blast crisis chronic myelogenous leukemia and Philadelphia chromosome-positive acute lymphocytic leukemia. J Clin Invest. 2007;117(9):2408-2421.
35. Iervolino A, Santilli G, Trotta R, et al. hnRNP A1 nucleocytoplasmic shuttling activity is required for normal myelopoiesis and BCR/ABL leukemogenesis. Mol Cell Biol. 2002;22(7): 2255-2266.
36. Azmi AS, Aboukameel A, Bao B, et al. Selective inhibitors of nuclear export block pancreatic cancer cell proliferation and reduce tumor growth in mice. Gastroenterology. 2013;144(2):447-456.
37. Tai YT, Landesman Y, Acharya C, et al. CRM1 inhibition induces tumor cell cytotoxicity and impairs osteoclastogenesis in multiple myeloma: molecular mechanisms and therapeutic implications [published online ahead of print April 16, 2013]. Leukemia.
38. la Cour T, Kiemer L, Mølgaard A, Gupta R, Skriver K, Brunak S. Analysis and prediction of leucine-rich nuclear export signals. Protein Eng Des Sel. 2004;17(6):527-536.
39. Vigneri P, Wang JY. Induction of apoptosis in chronic myelogenous leukemia cells through nuclear entrapment of BCR-ABL tyrosine kinase. Nat Med. 2001;7(2):228-234.
40. Gallouzi IE, Brennan CM, Steitz JA. Protein ligands mediate the CRM1-dependent export of HuR in response to heat shock. RNA. 2001;7(9): 1348-1361.
41. Lucas CM, Harris RJ, Giannoudis A, Copland M, Slupsky JR, Clark RE. Cancerous inhibitor of PP2A (CIP2A) at diagnosis of chronic myeloid leukemia is a critical determinant of disease progression. Blood. 2011;117(24): 6660-6668.
42. Koptyra M, Cramer K, Slupianek A, Richardson C, Skorski T. BCR/ABL promotes accumulation of chromosomal aberrations induced by oxidative and genotoxic stress. Leukemia. 2008;22(10): 1969-1972.
43. Stoklosa T, Poplawski T, Koptyra M, et al. BCR/ABL inhibits mismatch repair to protect from apoptosis and induce point mutations. Cancer Res. 2008;68(8):2576-2580.
44. Thakar K, Karaca S, Port SA, Urlaub H, Kehlenbach RH. Identification of CRM1-dependent Nuclear Export Cargos Using Quantitative Mass Spectrometry. Mol Cell Proteomics. 2013;12(3):664-678.
45. Kalid O, Toledo Warshaviak D, Shechter S, Sherman W, Shacham S. Consensus Induced Fit Docking (cIFD): methodology, validation, and application to the discovery of novel Crm1 inhibitors. J Comput Aided Mol Des. 2012;26(11): 1217-1228.
46. Razak JRA, Soerensen MM, Mahipal A, et al. First-in-class, first-in-human phase I trial of KPT-330, a selective inhibitor of nuclear export (SINE) in patients (pts) with advanced solid tumors [abstract]. J Clin Oncol. 2013;31 (Suppl). Abstract 2505.
47. Kancha RK, von Bubnoff N, Miething C, Peschel C, Götze KS, Duyster J. Imatinib and leptomycin B are effective in overcoming imatinib-resistance due to Bcr-Abl amplification and clonal evolution but not due to Bcr-Abl kinase domain mutation. Haematologica. 2008;93(11):1718-1722.
48. Newlands ES, Rustin GJ, Brampton MH. Phase I trial of elactocin. Br J Cancer. 1996;74(4): 648-649.
49. Samanta AK, Chakraborty SN, Wang Y, et al. Jak2 inhibition deactivates Lyn kinase through the SET-PP2A-SHP1 pathway, causing apoptosis in drug-resistant cells from chronic myelogenous leukemia patients. Oncogene. 2009;28(14):1669-1681.
50. Michael WM, Choi M, Dreyfuss G. A nuclear export signal in hnRNP A1: a signalmediated, temperature-dependent nuclear protein export pathway. Cell. 1995;83(3): 415-422.
51. Perrotti D, Neviani P. Protein phosphatase 2A: a target for anticancer therapy. Lancet Oncol. 2013;14(6):e229-e238.
52. Azmi AS, Al-Katib A, Aboukameel A, et al. Selective inhibitors of nuclear export for the treatment of non-Hodgkin's lymphomas. Haematologica. 2013;98(7):1098-1106.