Janus kinase inhibitor INCB20 has antiproliferative and apoptotic effects on human myeloma cells in vitro and in vivo

Molecular Cancer Therapeutics

Volumn 8, Issue 1, 2009, Pages 26-35

  Burger, Renate ^a,b   Le Gouill, Steven ^a   Tai, Yu Tzu ^a   Shringarpure, Reshma ^a   Tassone, Pierfrancesco ^a   Neri, Paola ^a   Podar, Klaus ^a   Catley, Laurence ^a   Hideshima, Teru ^a   Chauhan, Dharminder ^a   Caulder, Eian ^c   Neilan, Claire L ^c   Vaddi, Kris ^c   Li, Jun ^c   Gramatzki, Martin ^b   Fridman, Jordan S ^c   Anderson, Kenneth C ^a  

^a HARVARD MEDICAL SCHOOL   (United States)

^b UNIVERSITY OF KIEL   (Germany)

^c Experimental Station   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

DEXAMETHASONE; INCB 20; INTERLEUKIN 6; JANUS KINASE INHIBITOR; PROTEIN KINASE B; PROTEIN TYROSINE KINASE; SOMATOMEDIN C; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANTINEOPLASTIC ACTIVITY; APOPTOSIS; ARTICLE; CANCER GROWTH; CELL GROWTH; CELL SURVIVAL; CONTROLLED STUDY; DRUG EFFICACY; EMBRYO; GROWTH INHIBITION; HEMATOPOIETIC STEM CELL; HUMAN; HUMAN CELL; IC 50; IN VITRO STUDY; IN VIVO STUDY; MOUSE; MULTIPLE MYELOMA; MYELOMA CELL; NONHUMAN; PRIORITY JOURNAL; PROTEIN PHOSPHORYLATION;

ANIMALS; ANTINEOPLASTIC AGENTS; APOPTOSIS; BONE MARROW CELLS; CELL PROLIFERATION; CELLS, CULTURED; COCULTURE TECHNIQUES; CYTOPROTECTION; DEXAMETHASONE; HUMANS; INTERLEUKIN-6; JANUS KINASES; MICE; MULTIPLE MYELOMA; PHOSPHORYLATION; PROTEIN KINASE INHIBITORS; STAT3 TRANSCRIPTION FACTOR; STROMAL CELLS; SUBSTRATE SPECIFICITY; SURVIVAL RATE; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 58149488636     PISSN: 15357163     EISSN: None     Source Type: Journal    
DOI: 10.1158/1535-7163.MCT-08-0149     Document Type: Article

References (49)

1. Leonard WJ, O'Shea JJ. Jaks and STATs: biological implications. Annu Rev Immunol 1998;16:293-322.
2. Rane SG, Reddy EP. Janus kinases: components of multiple signaling pathways. Oncogene 2000;19:5662-79.
3. Ward AC, Touw I, Yoshimura A. The Jak-Stat pathway in normal and perturbed hematopoiesis. Blood 2000;95:19-29.
4. Verma A, Kambhampati S, Parmar S, Platanias LC. Jak family of kinases in cancer. Cancer Metastasis Rev 2003;22:423-34.
5. Lacronique V, Boureux A, Valle VD, et al. A TEL-JAK2 fusion protein with constitutive kinase activity in human leukemia. Science 1997;278:1309-12.
6. Peeters P, Raynaud SD, Cools J, et al. Fusion of TEL, the ETS-variant gene 6 (ETV6), to the receptor-associated kinase JAK2 as a result of t(9;12) in a lymphoid and t(9;15;12) in a myeloid leukemia. Blood 1997;90:2535-40.
7. Carron C, Cormier F, Janin A, et al. TEL-JAK2 transgenic mice develop T-cell leukemia. Blood 2000;95:3891-9.
8. Levine RL, Wadleigh M, Cools J, et al. Activating mutation in the tyrosine kinase JAK2 in polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis. Cancer Cell 2005;7:387-97.
9. Klein B, Zhang XG, Lu ZY, Bataille R. Interleukin-6 in human multiple myeloma. Blood 1995;85:863-72.
10. Hideshima T, Bergsagel PL, Kuehl WM, Anderson KC. Advances in biology of multiple myeloma: clinical applications. Blood 2004;104:607-18.
11. Heinrich PC, Behrmann I, Haan S, Hermanns HM, Muller-Newen G, Schaper F. Principles of interleukin (IL)-6-type cytokine signalling and its regulation. Biochem J 2003;374:1-20.
12. Berger LC, Hawley TS, Lust JA, Goldman SJ, Hawley RG. Tyrosine phosphorylation of JAK-TYK kinases in malignant plasma cell lines growth-stimulated by interleukins 6 and 11. Biochem Biophys Res Commun 1994;202:596-605.
13. Stahl N, Boulton TG, Farruggella T, et al. Association and activation of Jak-Tyk kinases by CNTF-LIF-OSM-IL-6h receptor components. Science 1994;263:92-5.
14. Ogata A, Chauhan D, Teoh G, et al. IL-6 triggers cell growth via the Ras-dependent mitogen-activated protein kinase cascade. J Immunol 1997;159:2212-21.
15. Hideshima T, Chauhan D, Teoh G, et al. Characterization of signaling cascades triggered by human interleukin-6 versus Kaposi's sarcoma-associated herpes virus-encoded viral interleukin 6. Clin Cancer Res 2000;6:1180-9.
16. Rawat R, Rainey GJ, Thompson CD, Frazier-Jessen MR, Brown RT, Nordan RP. Constitutive activation of STAT3 is associated with the acquisition of an interleukin 6-independent phenotype by murine plasmacytomas and hybridomas. Blood 2000;96:3514-21.
17. De Vos J, Jourdan M, Tarte K, Jasmin C, Klein B. JAK2 tyrosine kinase inhibitor tyrphostin AG490 downregulates the mitogen-activated protein kinase (MAPK) and signal transducer and activator of transcription (STAT) pathways and induces apoptosis in myeloma cells. Br J Haematol 2000;109:823-8.
18. Tani Y, Nishimoto N, Ogata A, Shima Y, Yoshizaki K, Kishimoto T. Gp130 in human myeloma/plasmacytoma. Curr Top Microbiol Immunol 1995;194:229-33.
19. Burger R, Bakker F, Guenther A, et al. Functional significance of novel neurotrophin-1/B cell-stimulating factor-3 (cardiotrophin-like cytokine) for human myeloma cell growth and survival. Br J Haematol 2003;123:869-78.
20. Burger R, Neipel F, Fleckenstein B, et al. Human herpesvirus type 8 interleukin-6 homologue is functionally active on human myeloma cells. Blood 1998;91:1858-63.
21. Brenne AT, Ro TB, Waage A, Sundan A, Borset M, Hjorth-Hansen H. Interleukin-21 is a growth and survival factor for human myeloma cells. Blood 2002;99:3756-62.
22. Burger R, Guenther A, Bakker F, et al. Gp130 and ras mediated signaling in human plasma cell line INA-6: a cytokine-regulated tumor model for plasmacytoma. Hematol J 2001;2:42-53.
23. Tai YT, Teoh G, Shima Y, et al. Isolation and characterization of human multiple myeloma cell enriched populations. J Immunol Methods 2000;235:11-9.
24. Hönemann D, Chatterjee M, Savino R, et al. The IL-6 receptor antagonist SANT-7 overcomes bone marrow stromal cell-mediated drug resistance of multiple myeloma cells. Int J Cancer 2001;93:674-80.
25. Fridman S, Li J, Liu P, et al. Discovery and preclinical development of selective JAK inhibitors for the treatment of haematological malignancies. Haematologica 2007;92:117.
26. Yaccoby S, Barlogie B, Epstein J. Primary myeloma cells growing in SCID-hu mice: a model for studying the biology and treatment of myeloma and its manifestations. Blood 1998;92:2908-13.
27. Chauhan D, Pandey P, Hideshima T, et al. SHP2 mediates the protective effect of interleukin-6 against dexamethasone-induced apoptosis in multiple myeloma cells. J Biol Chem 2000;275:27845-50.
28. Hideshima T, Nakamura N, Chauhan D, Anderson KC. Biologic sequelae of interleukin-6 induced PI3-K/Akt signaling in multiple myeloma. Oncogene 2001;20:5991-6000.
29. LeRoith D, Roberts CT, Jr. The insulin-like growth factor system and cancer. Cancer Lett 2003;195:127-37.
30. Catlett-Falcone R, Landowski TH, Oshiro MM, et al. Constitutive activation of Stat3 signaling confers resistance to apoptosis in human U266 myeloma cells. Immunity 1999;10:105-15.
31. Quintanilla-Martinez L, Kremer M, Specht K, et al. Analysis of signal transducer and activator of transcription 3 (Stat 3) pathway in multiple myeloma: Stat 3 activation and cyclin D1 dysregulation are mutually exclusive events. Am J Pathol 2003;162:1449-61.
32. + cells derived from multiple myeloma patients, and suppression of these transcription factors leads to apoptosis. Blood 2004;103:3175-84.
33. Pedranzini L, Dechow T, Berishaj M, et al. Pyridone 6, a pan-Janus-activated kinase inhibitor, induces growth inhibition of multiple myeloma cells. Cancer Res 2006;66:9714-21.
34. Puthier D, Bataille R, Amiot M. IL-6 up-regulates mcl-1 in human myeloma cells through JAK/STAT rather than ras/MAPkinase pathway. Eur J Immunol 1999;29:3945-50.
35. Hirano T, Ishihara K, Hibi M. Roles of STAT3 in mediating the cell growth, differentiation and survival signals relayed through the IL-6 family of cytokine receptors. Oncogene 2000;19:2548-56.
36. Bowman T, Garcia R, Turkson J, Jove R. STATs in oncogenesis. Oncogene 2000;19:2474-88.
37. Brocke-Heidrich K, Kretzschmar AK, Pfeifer G, et al. Interleukin-6- dependent gene expression profiles in multiple myeloma INA-6 cells reveal a Bcl-2 family-independent survival pathway closely associated with Stat3 activation. Blood 2004;103:242-51.
38. Alas S, Bonavida B. Inhibition of constitutive STAT3 activity sensitizes resistant non-Hodgkin's lymphoma and multiple myeloma to chemotherapeutic drug-mediated apoptosis. Clin Cancer Res 2003;9:316-26.
39. Tu Y, Gardner A, Lichtenstein A. The phosphatidylinositol 3-kinase/AKT kinase pathway in multiple myeloma plasma cells: roles in cytokine-dependent survival and proliferative responses. Cancer Res 2000;60:6763-70.
40. Bataille R, Barlogie B, Lu ZY, et al. Biologic effects of anti-interleukin-6 murine monoclonal antibody in advanced multiple myeloma. Blood 1995;86:685-91.
41. van Zaanen HC, Lokhorst HM, Aarden LA, et al. Chimaeric antiinterleukin 6 monoclonal antibodies in the treatment of advanced multiple myeloma: a phase I dose-escalating study. Br J Haematol 1998;102:783-90.
42. Tsunenari T, Koishihara Y, Nakamura A, et al. New xenograft model of multiple myeloma and efficacy of a humanized antibody against human interleukin-6 receptor. Blood 1997;90:2437-44.
43. Sporeno E, Savino R, Ciapponi L, et al. Human interleukin-6 receptor super-antagonists with high potency and wide spectrum on multiple myeloma cells. Blood 1996;87:4510-9.
44. Silvestris F, Lombardi L, De Matteo M, Bruno A, Dammacco F. Myeloma bone disease: pathogenetic mechanisms and clinical assessment. Leuk Res 2007;31:129-38.
45. Lu ZY, Brailly H, Wijdenes J, Bataille R, Rossi JF, Klein B. Measurement of whole body interleukin-6 (IL-6) production: prediction of the efficacy of anti-IL-6 treatments. Blood 1995;86:3123-31.
46. O'Shea JJ, Pesu M, Borie DC, Changelian PS. A new modality for immunosuppression: targeting the JAK/STAT pathway. Nat Rev Drug Discov 2004;3:555-64.
47. Paniagua R, Si MS, Flores MG, et al. Effects of JAK3 inhibition with CP-690,550 on immune cell populations and their functions in nonhuman primate recipients of kidney allografts. Transplantation 2005;80:1283-92.
48. Treon SP, Pilarski LM, Belch AR, et al. CD20-directed serotherapy in patients with multiple myeloma: biologic considerations and therapeutic applications. J Immunother 2002;25:72-81.
49. Wilkinson B, Gaweco A, Changelian P, et al. Improvement in psoriatic lesions during a 14-day trial of CP-690,550 (CP), an orally active inhibitor of Janus kinase 3 (JAK3). Ann Rheum Dis 2007;66:155.