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

British Journal of Haematology

Volumn 161, Issue 1, 2013, Pages 117-127

  Etchin, Julia ^a,b   Sanda, Takaomi ^a,b   Mansour, Marc R ^a,b   Kentsis, Alex ^a,b   Montero, Joan ^a,c   Le, Bonnie T ^a,b   Christie, Amanda L ^a,b   Mccauley, Dilara ^d   Rodig, Scott J ^a,b   Kauffman, Michael ^d   Shacham, Sharon ^d   Stone, Richard ^a,c   Letai, Anthony ^a,c   Kung, Andrew L ^a,b   Thomas Look, A ^a,b  

^a DANA FARBER CANCER INSTITUTE   (United States)

^b BOSTON CHILDREN S HOSPITAL   (United States)

^c HARVARD MEDICAL SCHOOL   (United States)

^d Karyopharm Therapeutics   (United States)

Author keywords

Acute leukaemia; All; Aml; New drugs for leukaemia; New drugs for lymphoma

Indexed keywords

CYCLIN DEPENDENT KINASE INHIBITOR 2A; EXPORTIN 1; KPT 330; LIPOCORTIN 5; NOTCH1 RECEPTOR; PHOSPHATIDYLINOSITOL 3,4,5 TRISPHOSPHATE 3 PHOSPHATASE; PROTEIN INHIBITOR; PROTEIN P53; TRANSCRIPTION FACTOR TAL1; TUMOR SUPPRESSOR PROTEIN; UNCLASSIFIED DRUG;

ACUTE GRANULOCYTIC LEUKEMIA; ACUTE LYMPHOBLASTIC LEUKEMIA; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANTILEUKEMIC ACTIVITY; APOPTOSIS; ARTICLE; CELL ACTIVITY; CELL CYCLE; CELL CYCLE G1 PHASE; CELL CYCLE PROGRESSION; CONTROLLED STUDY; DRUG ACTIVITY; DRUG MECHANISM; DRUG TARGETING; FEMALE; HEMATOPOIETIC CELL; IC 50; IN VIVO STUDY; MOUSE; NONHUMAN; NUCLEAR EXPORT SIGNAL; PRIORITY JOURNAL; T CELL LEUKEMIA;

ACTIVE TRANSPORT, CELL NUCLEUS; ANIMALS; ANTINEOPLASTIC AGENTS; APOPTOSIS; BLOOD CELLS; CELL CYCLE CHECKPOINTS; CELL LINE, TUMOR; CELL NUCLEUS; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG SCREENING ASSAYS, ANTITUMOR; FEMALE; HUMANS; KARYOPHERINS; LEUKEMIA, MYELOID, ACUTE; MICE; MICE, INBRED NOD; MICE, SCID; NUCLEAR PROTEINS; PRECURSOR T-CELL LYMPHOBLASTIC LEUKEMIA-LYMPHOMA; RECEPTORS, CYTOPLASMIC AND NUCLEAR; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 84875052270     PISSN: 00071048     EISSN: 13652141     Source Type: Journal    
DOI: 10.1111/bjh.12231     Document Type: Article

References (42)

1. Armstrong, S.A. & Look, A.T. (2005) Molecular genetics of acute lymphoblastic leukemia. Journal of Clinical Oncology, 23, 6306-6315.
2. Bonazzi, S., Eidam, O., Guttinger, S., Wach, J.Y., Zemp, I., Kutay, U. & Gademann, K. (2010) Anguinomycins and derivatives: total syntheses, modeling, and biological evaluation of the inhibition of nucleocytoplasmic transport. Journal of the American Chemical Society, 132, 1432-1442.
3. Daelemans, D., Afonina, E., Nilsson, J., Werner, G., Kjems, J., De Clercq, E., Pavlakis, G.N. & Vandamme, A.M. (2002) A synthetic HIV-1 Rev inhibitor interfering with the CRM1-mediated nuclear export. Proceedings of the National Academy of Sciences of the United States of America, 99, 14440-14445.
4. Del Gaizo Moore, V. & Letai, A. (2012) BH3 profiling - Measuring integrated function of the mitochondrial apoptotic pathway to predict cell fate decisions. Cancer Letters. [Epub ahead of print] doi:10.1016/j.canlet.2011.12.021
5. Dong, X., Biswas, A., Suel, K.E., Jackson, L.K., Martinez, R., Gu, H. & Chook, Y.M. (2009) Structural basis for leucine-rich nuclear export signal recognition by CRM1. Nature, 458, 1136-1141.
6. Etchin, J., Sun, Q., Kentsis, A., Farmer, A., Zhang, Z.C., Sanda, T., Mansour, M.R., Barcelo, C., McCauley, D., Kauffman, M., Shacham, S., Christie, A.L., Kung, A.L., Rodig, S.J., Chook, Y.M. & Look, A.T. (2012) Anti-leukemic activity of nuclear export inhibitors that spare normal hematopoietic cells. Leukemia, 27, 66-74.
7. Ferrando, A.A. & Look, A.T. (2003) Gene expression profiling in T-cell acute lymphoblastic leukemia. Seminars in Hematology, 40, 274-280.
8. Forbes, S.A., Bhamra, G., Bamford, S., Dawson, E., Kok, C., Clements, J., Menzies, A., Teague, J.W., Futreal, P.A. & Stratton, M.R. (2008) The Catalogue of Somatic Mutations in Cancer (COSMIC). Current protocols in human genetics, Chapter 10, Unit 10-11.
9. Forbes, S.A., Bindal, N., Bamford, S., Cole, C., Kok, C.Y., Beare, D., Jia, M., Shepherd, R., Leung, K., Menzies, A., Teague, J.W., Campbell, P.J., Stratton, M.R. & Futreal, P.A. (2011) COSMIC: mining complete cancer genomes in the Catalogue of Somatic Mutations in Cancer. Nucleic Acids Research, 39, D945-D950.
10. Fornerod, M., Ohno, M., Yoshida, M. & Mattaj, I.W. (1997) CRM1 is an export receptor for leucine-rich nuclear export signals. Cell, 90, 1051-1060.
11. Fukuda, M., Asano, S., Nakamura, T., Adachi, M. & Yoshida, M. (1997) CRM1 is responsible for intracellular transport meditted by the nuclear export signal. Nature, 390, 308-311.
12. Guttler, T., Madl, T., Neumann, P., Deichsel, D., Corsini, L., Monecke, T., Ficner, R., Sattler, M. & Gorlich, D. (2010) NES consensus redefined by structures of PKI-type and Rev-type nuclear export signals bound to CRM1. Nature Structural & Molecular Biology, 17, 1367-1376.
13. Huang, W.Y., Yue, L., Qiu, W.S., Wang, L.W., Zhou, X.H. & Sun, Y.J. (2009) Prognostic value of CRM1 in pancreas cancer. Clinical and Investigative Medicine, 32, E315.
14. Kudo, N., Matsumori, N., Taoka, H., Fujiwara, D., Schreiner, E.P., Wolff, B., Yoshida, M. & Horinouchi, S. (1999) Leptomycin B inactivates CRM1/exportin 1 by covalent modification at a cysteine residue in the central conserved region. Proceedings of the National Academy of Sciences of the United States of America, 96, 9112-9117.
15. Lapalombella, R., Sun, Q., Williams, K., Tangeman, L., Jha, S., Zhong, Y., Goettl, V., Mahoney, E., Berglund, C., Gupta, S., Farmer, A., Mani, R., Johnson, A.J., Lucas, D., Mo, X., Daelemans, D., Sandanayaka, V., Shechter, S., McCauley, D., Shacham, S., Kauffman, M., Chook, Y.M. & Byrd, J.C. (2012) Selective inhibitors of nuclear export (SINE) show that CRM1/XPO1 is a target in chronic lymphocytic leukemia. Blood, 120, 4621-4634.
16. Martins, C.P., Brown-Swigart, L. & Evan, G.I. (2006) Modeling the therapeutic efficacy of p53 restoration in tumors. Cell, 127, 1323-1334.
17. Maser, R.S., Choudhury, B., Campbell, P.J., Feng, B., Wong, K.K., Protopopov, A., O'Neil, J., Gutierrez, A., Ivanova, E., Perna, I., Lin, E., Mani, V., Jiang, S., McNamara, K., Zaghlul, S., Edkins, S., Stevens, C., Brennan, C., Martin, E.S., Wiedemeyer, R., Kabbarah, O., Nogueira, C., Histen, G., Aster, J., Mansour, M., Duke, V., Foroni, L., Fielding, A.K., Goldstone, A.H., Rowe, J.M., Wang, Y.A., Look, A.T., Stratton, M.R., Chin, L., Futreal, P.A. & DePinho, R.A. (2007) Chromosomally unstable mouse tumours have genomic alterations similar to diverse human cancers. Nature, 447, 966-971.
18. Meissner, T., Krause, E. & Vinkemeier, U. (2004) Ratjadone and leptomycin B block CRM1-dependent nuclear export by identical mechanisms. FEBS Letters, 576, 27-30.
19. Monecke, T., Guttler, T., Neumann, P., Dickmanns, A., Gorlich, D. & Ficner, R. (2009) Crystal structure of the nuclear export receptor CRM1 in complex with Snurportin1 and RanGTP. Science, 324, 1087-1091.
20. Mutka, S.C., Yang, W.Q., Dong, S.D., Ward, S.L., Craig, D.A., Timmermans, P.B. & Murli, S. (2009) Identification of nuclear export inhibitors with potent anticancer activity in vivo. Cancer Research, 69, 510-517.
21. Noske, A., Weichert, W., Niesporek, S., Roske, A., Buckendahl, A.C., Koch, I., Sehouli, J., Dietel, M. & Denkert, C. (2008) Expression of the nuclear export protein chromosomal region maintenance/exportin 1/Xpo1 is a prognostic factor in human ovarian cancer. Cancer, 112, 1733-1743.
22. O'Neil, J., Tchinda, J., Gutierrez, A., Moreau, L., Maser, R.S., Wong, K.K., Li, W., McKenna, K., Liu, X.S., Feng, B., Neuberg, D., Silverman, L., DeAngelo, D.J., Kutok, J.L., Rothstein, R., DePinho, R.A., Chin, L., Lee, C. & Look, A.T. (2007) Alu elements mediate MYB gene tandem duplication in human T-ALL. Journal of Experimental Medicine, 204, 3059-3066.
23. Ossareh-Nazari, B., Bachelerie, F. & Dargemont, C. (1997) Evidence for a role of CRM1 in signal-mediated nuclear protein export. Science, 278, 141-144.
24. Palomero, T., Sulis, M.L., Cortina, M., Real, P.J., Barnes, K., Ciofani, M., Caparros, E., Buteau, J., Brown, K., Perkins, S.L., Bhagat, G., Agarwal, A.M., Basso, G., Castillo, M., Nagase, S., Cordon-Cardo, C., Parsons, R., Zuniga-Pflucker, J.C., Dominguez, M. & Ferrando, A.A. (2007) Mutational loss of PTEN induces resistance to NOTCH1 inhibition in T-cell leukemia. Nature Medicine, 13, 1203-1210.
25. Pui, C.H. & Evans, W.E. (2006) Treatment of acute lymphoblastic leukemia. New England Journal of Medicine, 354, 166-178.
26. Pui, C.H., Robison, L.L. & Look, A.T. (2008) Acute lymphoblastic leukaemia. Lancet, 371, 1030-1043.
27. Ranganathan, P., Yu, X., Na, C., Santhanam, R., Shacham, S., Kauffman, M., Walker, A., Klisovic, R., Blum, W., Caligiuri, M., Croce, C.M., Marcucci, G. & Garzon, R. (2012) Pre-clinical activity of a novel CRM1 inhibitor in acute myeloid leukemia. Blood, 120, 1765-1773.
28. Ryan, J.A., Brunelle, J.K. & Letai, A. (2010) Heightened mitochondrial priming is the basis for apoptotic hypersensitivity of CD4 + CD8 + thymocytes. Proceedings of the National Academy of Sciences of the United States of America, 107, 12895-12900.
29. Sakakibara, K., Saito, N., Sato, T., Suzuki, A., Hasegawa, Y., Friedman, J.M., Kufe, D.W., Vonhoff, D.D., Iwami, T. & Kawabe, T. (2011) CBS9106 is a novel reversible oral CRM1 inhibitor with CRM1 degrading activity. Blood, 118, 3922-3931.
30. Shen, A., Wang, Y., Zhao, Y., Zou, L., Sun, L. & Cheng, C. (2009) Expression of CRM1 in human gliomas and its significance in p27 expression and clinical prognosis. Neurosurgery, 65, discussion 153-159.
31. Siddiqui, N. & Borden, K.L. (2012) mRNA export and cancer. Wiley interdisciplinary reviews. RNA, 3, 13-25.
32. Turner, J.G., Marchion, D.C., Dawson, J.L., Emmons, M.F., Hazlehurst, L.A., Washausen, P. & Sullivan, D.M. (2009) Human multiple myeloma cells are sensitized to topoisomerase II inhibitors by CRM1 inhibition. Cancer Research, 69, 6899-6905.
33. Turner, J.G., Dawson, J. & Sullivan, D.M. (2012) Nuclear export of proteins and drug resistance in cancer. Biochemical Pharmacology, 83, 1021-1032.
34. Van Neck, T., Pannecouque, C., Vanstreels, E., Stevens, M., Dehaen, W. & Daelemans, D. (2008) Inhibition of the CRM1-mediated nucleocytoplasmic transport by N-azolylacrylates: structure-activity relationship and mechanism of action. Bioorganic & Medicinal Chemistry, 16, 9487-9497.
35. Ventura, A., Kirsch, D.G., McLaughlin, M.E., Tuveson, D.A., Grimm, J., Lintault, L., Newman, J., Reczek, E.E., Weissleder, R. & Jacks, T. (2007) Restoration of p53 function leads to tumour regression in vivo. Nature, 445, 661-665.
36. Wach, J.Y., Guttinger, S., Kutay, U. & Gademann, K. (2010) The cytotoxic styryl lactone goniothalamin is an inhibitor of nucleocytoplasmic transport. Bioorganic & Medicinal Chemistry Letters, 20, 2843-2846.
37. van der Watt, P.J., Maske, C.P., Hendricks, D.T., Parker, M.I., Denny, L., Govender, D., Birrer, M.J. & Leaner, V.D. (2009) The Karyopherin proteins, Crm1 and Karyopherin beta1, are overexpressed in cervical cancer and are critical for cancer cell survival and proliferation. International Journal of Cancer, 124, 1829-1840.
38. Weng, A.P., Ferrando, A.A., Lee, W., Morris, J.P.t., Silverman, L.B., Sanchez-Irizarry, C., Blacklow, S.C., Look, A.T. & Aster, J.C. (2004) Activating mutations of NOTCH1 in human T cell acute lymphoblastic leukemia. Science, 306, 269-271.
39. Xu, D., Farmer, A. & Chook, Y.M. (2010) Recognition of nuclear targeting signals by Karyopherin-beta proteins. Current Opinion in Structural Biology, 20, 782-790.
40. Xu, D., Grishin, N.V. & Chook, Y.M. (2012a) NESdb: a database of NES-containing CRM1 cargos. Molecular Biology of the Cell, 23, 3673-3676.
41. Xu, D., Farmer, A., Collett, G., Grishin, N.V. & Chook, Y.M. (2012b) Sequence and structural analyses of nuclear export signals in the NESdb database. Molecular Biology of the Cell, 23, 3677-3693.
42. Yao, Y., Dong, Y., Lin, F., Zhao, H., Shen, Z., Chen, P., Sun, Y.J., Tang, L.N. & Zheng, S.E. (2009) The expression of CRM1 is associated with prognosis in human osteosarcoma. Oncology Reports, 21, 229-235.