What is next beyond janus kinase 2 inhibitors for primary myelofibrosis?

Current Opinion in Hematology

Volumn 20, Issue 2, 2013, Pages 123-129

  Santos, Fabio P S ^a   Verstovsek, Srdan ^b  

^a HOSPITAL ISRAELITA ALBERT EINSTEIN   (Brazil)

^b UNIVERSITY OF TEXAS MD ANDERSON CANCER CENTER   (United States)

Author keywords

heat shock protein 90 inhibitor; histone deacetylase inhibitor; lysyl oxidase like enzyme inhibitor; myelofibrosis; signal transducer and activator of transcription 5 inhibitor

Indexed keywords

AB 0024; ALISERTIB; ANTINEOPLASTIC AGENT; AURORA A KINASE; AUY 992; BCR ABL PROTEIN; CD135 ANTIGEN; FRESOLIMUMAB; HEAT SHOCK PROTEIN 90 INHIBITOR; HISTONE DEACETYLASE INHIBITOR; JANUS KINASE 2 INHIBITOR; LYSYL OXIDASE LIKE 2; MONOCLONAL ANTIBODY; PANOBINOSTAT; PIMOZIDE; PUH 71; RUXOLITINIB; STAT3 PROTEIN; STAT5 PROTEIN; TANESPIMYCIN; TRANSFORMING GROWTH FACTOR ALPHA; TRANSFORMING GROWTH FACTOR BETA; UNCLASSIFIED DRUG;

APOPTOSIS; CELL PROLIFERATION; CELL VIABILITY; CYTOKINE PRODUCTION; DRUG MECHANISM; ENZYME INHIBITION; HUMAN; MAXIMUM TOLERATED DOSE; MYELOFIBROSIS; MYELOID METAPLASIA; NONHUMAN; POLYCYTHEMIA VERA; PRIORITY JOURNAL; PROTEIN EXPRESSION; REVIEW; SPLENOMEGALY; THROMBOCYTOPENIA; TREATMENT DURATION;

HUMANS; JANUS KINASE 2; PRIMARY MYELOFIBROSIS; PROTEIN KINASE INHIBITORS;

EID: 84873356250     PISSN: 10656251     EISSN: 15317048     Source Type: Journal    
DOI: 10.1097/MOH.0b013e32835d8e10     Document Type: Review

References (43)

1. Santos FP, Verstovsek S. Therapy with JAK2 inhibitors for myeloproliferative neoplasms. Hematol Oncol Clin North Am 2012; 26:1083-1099.
2. 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; 7:387-397.
3. Kralovics R, Passamonti F, Buser AS, et al. A gain-of-function mutation of JAK2 in myeloproliferative disorders. N Engl J Med 2005; 352:1779-1790.
4. James C, Ugo V, Le Couedic JP, et al. A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera. Nature 2005; 434:1144-1148.
5. Baxter EJ, Scott LM, Campbell PJ, et al. Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders. Lancet 2005; 365:1054-1061.
6. Verstovsek S, Mesa RA, Gotlib J, et al. A double-blind, placebo-controlled trial of ruxolitinib for myelofibrosis. N Engl J Med 2012; 366:799-807.
7. Harrison C, Kiladjian JJ, Al-Ali HK, et al. JAK inhibition with ruxolitinib versus best available therapy for myelofibrosis. N Engl J Med 2012; 366:787-798.
8. Pardanani A, Gotlib JR, Jamieson C, et al. Safety and efficacy of TG101348, a selective JAK2 inhibitor, in myelofibrosis. J Clin Oncol 2011; 29:789-796.
9. Verstovsek S, Kantarjian H, Mesa RA, et al. Safety and efficacy of INCB018424, a JAK1 and JAK2 inhibitor, in myelofibrosis. N Engl J Med 2010; 363:1117-1127.
10. Santos FP, Kantarjian HM, Jain N, et al. Phase 2 study of CEP-701, an orally available JAK2 inhibitor, in patients with primary or postpolycythemia vera/essential thrombocythemia myelofibrosis. Blood 2010; 115:1131-1136.
11. Marubayashi S, Koppikar P, Taldone T, et al. HSP90 is a therapeutic target in JAK2-dependent myeloproliferative neoplasms in mice and humans. J Clin Invest 2010; 120:3578-3593.
12. Weigert O, Lane AA, Bird L, et al. Genetic resistance to JAK2 enzymatic inhibitors is overcome by HSP90 inhibition. J Exp Med 2012; 209:259-273.
13. Wang Y, Fiskus W, Chong DG, et al. Cotreatment with panobinostat and JAK2 inhibitor TG101209 attenuates JAK2V617F levels and signaling and exerts synergistic cytotoxic effects against human myeloproliferative neoplastic cells. Blood 2009; 114:5024-5033.
14. Baffert F, Evrot E, Ebel N, et al. Improved efficacy upon combined JAK1/2 and pan-deacetylase inhibition using ruxolitinib (INC424) and panobinostat (LBH589) in preclinical mouse models of JAK2V617F-driven disease [abstract]. Blood 2011; 118:798.
15. DeAngelo DJ, Spencer A, Fischer T, et al. Activity of oral panobinostat (LBH589) in patients with myelofibrosis [abstract]. Blood 2009; 114: 2898.
16. Mascarenhas J, Mercado A, Rodriguez A, et al. Prolonged low dose therapy with a pan-deacetylase inhibtor, panobinostat (LBH589), in patients with myelofibrosis [abstract]. Blood 2011; 118:794.
17. DeAngelo DJ, Tefferi A, Fiskus W, et al. A phase II trial of panobinostat, an orally available deacetylase inhibitor (DACi), in patients with primary myelofibrosis (PMF), post essential thrombocythemia (ET), and post polycythemia vera (PV) myelofibrosis [abstract]. Blood 2010; 116:630.
18. Eliades A, Papadantonakis N, Bhupatiraju A, et al. Control of megakaryocyte expansion and bone marrow fibrosis by lysyl oxidase. J Biol Chem 2011; 286:27630-27638.
19. Barry-Hamilton V, Spangler R, Marshall D, et al. Allosteric inhibition of lysyl oxidase-like-2 impedes the development of a pathologic microenvironment. Nat Med 2010; 16:1009-1017.
20. Wen Q, Goldenson B, Silver SJ, et al. Identification of regulators of polyploidization presents therapeutic targets for treatment of AMKL. Cell 2012; 150:575-589.
21. Wen QJ, Goldenson B, Malinge S, et al. Induction of megakaryocyte polyploidization in combination with JAK inhibition as a novel therapeutic strategy for myeloproliferative neoplasms. Blood 2011; 118: 64.
22. Nelson EA, Walker SR, Weisberg E, et al. The STAT5 inhibitor pimozide decreases survival of chronic myelogenous leukemia cells resistant to kinase inhibitors. Blood 2011; 117:3421-3429.
23. Bar-Natan M, Nelson EA, Walker SR, et al. Dual inhibition of Jak2 and STAT5 enhances killing of myeloproliferative neoplasia cells. Leukemia 2012; 26:1407-1410.
24. Trepel J, Mollapour M, Giaccone G, Neckers L. Targeting the dynamic HSP90 complex in cancer. Nat Rev Cancer 2010; 10:537-549.
25. Gorre ME, Ellwood-Yen K, Chiosis G, et al. BCR-ABL point mutants isolated from patients with imatinib mesylate-resistant chronic myeloid leukemia remain sensitive to inhibitors of the BCR-ABL chaperone heat shock protein 90. Blood 2002; 100:3041-3044.
26. George P, Bali P, Cohen P, et al. Cotreatment with 17-allylamino- demethoxygeldanamycin and FLT-3 kinase inhibitor PKC412 is highly effective against human acute myelogenous leukemia cells with mutant FLT-3. Cancer Res 2004; 64:3645-3652.
27. Bareng J, Jilani I, Gorre M, et al. A potential role for HSP90 inhibitors in the treatment of JAK2 mutant-positive diseases as demonstrated using quantitative flow cytometry. Leuk Lymphoma 2007; 48:2189-2195.
28. Koppikar P, Bhagwat N, Kilpivaara O, et al. Heterodimeric JAK-STAT activation as a mechanism of persistence to JAK2 inhibitor therapy. Nature 2012; 489:155-159.
29. Wang JC, Chen C, Dumlao T, et al. Enhanced histone deacetylase enzyme activity in primary myelofibrosis. Leuk Lymphoma 2008; 49:2321-2327.
30. Xu WS, Parmigiani RB, Marks PA. Histone deacetylase inhibitors: molecular mechanisms of action. Oncogene 2007; 26:5541-5552.
31. Verstovsek S, Estrov Z, Cortes JE, et al. The MD Anderson Cancer Center (MDACC) experience with ruxolitinib, an oral JAK1 and JAK2 inhibitor, in myelofibrosis: long-term follow-up outcomes of 107 patients from a phase I/II study [abstract]. Blood 2011; 118:3851.
32. Chagraoui H, Komura E, Tulliez M, et al. Prominent role of TGF-beta 1 in thrombopoietin-induced myelofibrosis in mice. Blood 2002; 100:3495-3503.
33. Villeval JL, Cohen-Solal K, Tulliez M, et al. High thrombopoietin production by hematopoietic cells induces a fatal myeloproliferative syndrome in mice. Blood 1997; 90:4369-4383.
34. Yan XQ, Lacey D, Hill D, et al. A model of myelofibrosis and osteosclerosis in mice induced by overexpressing thrombopoietin (mpl ligand): reversal of disease by bone marrow transplantation. Blood 1996; 88:402-409.
35. Kuter DJ, Mufti GJ, Bain BJ, et al. Evaluation of bone marrow reticulin formation in chronic immune thrombocytopenia patients treated with romiplostim. Blood 2009; 114:3748-3756.
36. Ciurea SO, Merchant D, Mahmud N, et al. Pivotal contributions of megakaryocytes to the biology of idiopathic myelofibrosis. Blood 2007; 110:986-993.
37. Papadantonakis N, Matsuura S, Ravid K. Megakaryocyte pathology and bone marrow fibrosis: the lysyl oxidase connection. Blood 2012; 120:1774-1781.
38. Kagan HM, Li W. Lysyl oxidase: properties, specificity, and biological roles inside and outside of the cell. J Cell Biochem 2003; 88:660-672.
39. Martyre MC, Le Bousse-Kerdiles MC, Romquin N, et al. Elevated levels of basic fibroblast growth factor in megakaryocytes and platelets from patients with idiopathic myelofibrosis. Br J Haematol 1997; 97:441-448.
40. Yu H, Jove R. The STATs of cancer-new molecular targets come of age. Nat Rev Cancer 2004; 4:97-105.
41. Takeda Y, Nakaseko C, Tanaka H, et al. Direct activation of STAT5 by ETV6-LYN fusion protein promotes induction of myeloproliferative neoplasm with myelofibrosis. Br J Haematol 2011; 153:589-598.
42. Yan D, Hutchison RE,Mohi G. Critical requirement for Stat5 in a mouse model of polycythemia vera. Blood 2012; 119:3539-3549.
43. Walz C, Ahmed W, Lazarides K, et al. Essential role for Stat5a/b in myeloproliferative neoplasms induced by BCR-ABL1 and JAK2(V617F) in mice. Blood 2012; 119:3550-3560.