Profile of pacritinib and its potential in the treatment of hematologic disorders

Journal of Blood Medicine

Volumn 5, Issue , 2014, Pages 143-152

  Hatzimichael, Eleftheria ^a   Tsolas, Evangelos ^a   Briasoulis, Evangelos ^a  

^a UNIVERSITY HOSPITAL OF IOANNINA   (Greece)

Author keywords

Acute myeloid leukemia; JAK inhibitors; Lymphoma; Myeloproliferative neoplasms; Pacritinib; SB 1518; Treatment

Indexed keywords

CCAAT ENHANCER BINDING PROTEIN; CD135 ANTIGEN; FIBROBLAST GROWTH FACTOR RECEPTOR 1; JANUS KINASE 2; LESTAURTINIB; NUCLEOPHOSMIN; PACRITINIB; PROGRAMMED DEATH 1 LIGAND 1; PROTEIN BCL XL; STAT PROTEIN; STAT5 PROTEIN; SUPPRESSOR OF CYTOKINE SIGNALING 1;

ABDOMINAL PAIN; ACUTE GRANULOCYTIC LEUKEMIA; ACUTE LYMPHOBLASTIC LEUKEMIA; ANEMIA; ANOREXIA; APOPTOSIS; B CELL LYMPHOMA; CONSTIPATION; COUGHING; DIARRHEA; DIZZINESS; DRUG SAFETY; DYSPNEA; FATIGUE; FEVER; GENE MUTATION; HEADACHE; HEMATOLOGIC DISEASE; HODGKIN DISEASE; HUMAN; INSOMNIA; MYELOFIBROSIS; MYELOID METAPLASIA; MYELOPROLIFERATIVE NEOPLASM; NAUSEA AND VOMITING; NONHUMAN; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); POLYCYTHEMIA VERA; PRURITUS; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; SIGNAL TRANSDUCTION; STOMACH DISTENSION; THROMBOCYTHEMIA; THROMBOCYTOPENIA;

EID: 84922337086     PISSN: None     EISSN: 11792736     Source Type: Journal    
DOI: 10.2147/JBM.S51253     Document Type: Review

References (57)

1. Harrison DA. The Jak/STAT pathway. Cold Spring Harb Perspect Biol. 2012; 4(3): a011205.
2. Furqan M, Akinleye A, Mukhi N, Mittal V Chen Y, Liu D. STAT inhibitors for cancer therapy. J Hematol Oncol. 2013; 6(1): 90.
3. Baxter EJ, Scott LM, Campbell PJ, et al; Cancer Genome Project. Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders. Lancet. 2005; 365(9464): 1054-1061.
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(7037): 1144-1148.
5. Steensma DP, Dewald GW, Lasho TL, et al. The JAK2 V617F activating tyrosine kinase mutation is an infrequent event in both "atypical" myeloproliferative disorders and myelodysplastic syndromes. Blood. 2005; 106(4): 1207-1209.
6. Scott LM, Campbell PJ, Baxter EJ, et al. The V617F JAK2 mutation is uncommon in cancers and in myeloid malignancies other than the classic myeloproliferative disorders. Blood. 2005;106(8):2920-2921.
7. Nangalia J, Massie CE, Baxter EJ, et al. Somatic CALR mutations in myeloproliferative neoplasms with nonmutated JAK2. N Engl J Med. 2013;369(25):2391-2405.
8. Klampfl T, Gisslinger H, Harutyunyan AS, et al. Somatic mutations of calreticulin in myeloproliferative neoplasms. N Engl J Med. 2013;369(25):2379-2390.
9. Ding BB, Yu JJ, Yu RY, et al. Constitutively activated STAT3 promotes cell proliferation and survival in the activated B-cell subtype of diffuse large B-cell lymphomas. Blood. 2008;111(3):1515-1523.
10. Green MR, Monti S, Rodig SJ, et al. Integrative analysis reveals selective 9p24.1 amplification, increased PD-1 ligand expression, and further induction via JAK2 in nodular sclerosing Hodgkin lymphoma and primary mediastinal large B-cell lymphoma. Blood. 2010;116(17): 3268-3277.
11. Rosenwald A, Wright G, Leroy K, et al. Molecular diagnosis of primary mediastinal B cell lymphoma identifies a clinically favorable subgroup of diffuse large B cell lymphoma related to Hodgkin lymphoma. J Exp Med. 2003;198(6):851-862.
12. Joos S, Küpper M, Ohl S, et al. Genomic imbalances including amplification of the tyrosine kinase gene JAK2 in CD30+ Hodgkin cells. Cancer Res. 2000;60(3):549-552.
13. Melzner I, Bucur AJ, Brüderlein S, et al. Biallelic mutation of SOCS-1 impairs JAK2 degradation and sustains phospho-JAK2 action in the MedB-1 mediastinal lymphoma line. Blood. 2005;105(6):2535-2542.
14. Weniger MA, Melzner I, Menz CK, et al. Mutations of the tumor suppressor gene SOCS-1 in classical Hodgkin lymphoma are frequent and associated with nuclear phospho-STAT5 accumulation. Oncogene. 2006;25(18):2679-2684.
15. Van Roosbroeck K, Cox L, Tousseyn T, et al. JAK2 rearrangements, including the novel SEC31A-JAK2 fusion, are recurrent in classical Hodgkin lymphoma. Blood. 2011;117(15):4056-4064.
16. Gupta M, Han JJ, Stenson M, et al. Elevated serum IL-10 levels in diffuse large B-cell lymphoma: a mechanism of aberrant JAK2 activation. Blood. 2012;119(12):2844-2853.
17. Aldinucci D, Gloghini A, Pinto A, De Filippi R, Carbone A. The classical Hodgkin's lymphoma microenvironment and its role in promoting tumour growth and immune escape. J Pathol. 2010;221(3):248-263.
18. Lee JW, Kim YG, Soung YH, et al. The JAK2 V617F mutation in de novo acute myelogenous leukemias. Oncogene. 2006;25(9):1434-1436.
19. Döhner K, Du J, Corbacioglu A, Scholl C, Schlenk RF, Döhner H. JAK2V617F mutations as cooperative genetic lesions in t(8;21)-positive acute myeloid leukemia. Haematologica. 2006;91(11):1569-1570.
20. Ikezoe T, Kojima S, Furihata M, et al. Expression of p-JAK2 predicts clinical outcome and is a potential molecular target of acute myelogenous leukemia. Int J Cancer. 2011;129(10):2512-2521.
21. Hatzimichael E, Georgiou G, Benetatos L, Briasoulis E. Gene mutations and molecularly targeted therapies in acute myeloid leukemia. Am J Blood Res. 2013;3(1):29-51.
22. Steensma DP, McClure RF, Karp JE, et al. JAK2 V617F is a rare finding in de novo acute myeloid leukemia, but STAT3 activation is common and remains unexplained. Leukemia. 2006;20(6):971-978.
23. Rosnet O, Schiff C, Pebusque MJ, et al. Human FLT3/FLK2 gene: cDNA cloning and expression in hematopoietic cells. Blood. 1993;82(4):1110-1119.
24. deLapeyriere O, Naquet P, Planche J, et al. Expression of Flt3 tyrosine kinase receptor gene in mouse hematopoietic and nervous tissues. Differentiation. 1995;58(5):351-359.
25. Zhang S, Mantel C, Broxmeyer HE. Flt3 signaling involves tyrosyl-phosphorylation of SHP-2 and SHIP and their association with Grb2 and Shc in Baf3/Flt3 cells. JLeukoc Biol. 1999;65(3):372-380.
26. Hart S, Goh KC, Novotny-Diermayr V, et al. Pacritinib (SB1518), a JAK2/FLT3 inhibitor for the treatment of acute myeloid leukemia. Blood Cancer J. 2011;1(11):e44.
27. Cervantes F, Dupriez B, Pereira A, et al. New prognostic scoring system for primary myelofibrosis based on a study of the International Working Group for Myelofibrosis Research and Treatment. Blood. 2009;113(13):2895-2901.
28. Guardiola P, Anderson JE, Bandini G, et al. Allogeneic stem cell transplantation for agnogenic myeloid metaplasia: A European Group for Blood and Marrow Transplantation, Societe Française de Greffe de Moelle, Gruppo Italiano per il Trapianto del Midollo Osseo, and Fred Hutchinson Cancer Research Center Collaborative Study. Blood. 1999;93(9):2831-2838.
29. Cervantes F, Alvarez-Lamm A, Domingo A, Arellano-Rodrigo E, Montserrat E. Efficacy and tolerability of danazol as a treatment for the anaemia of myelofibrosis with myeloid metaplasia: long-term results in 30 patients. Br J Haematol. 2005;129(6):771-775.
30. Mesa RA, Yao X, Cripe LD, et al. Lenalidomide and prednisone for myelofibrosis: Eastern Cooperative Oncology Group (ECOG) phase 2 trial E4903. Blood. 2010;116(22):4436-4438.
31. Verstovsek S, Mesa RA, Gotlib J, et al. A double-blind, placebo-controlled trial of ruxolitinib for myelofibrosis. N Engl J Med. 2012;366(9):799-807.
32. Döhner H, Estey EH, Amadori S, et al; European LeukemiaNet. Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet. Blood. 2010;115(3):t453-t474.
33. Fischer T, Stone RM, Deangelo DJ, et al. Phase IIB trial of oral Midostaurin (PKC412), the FMS-like tyrosine kinase 3 receptor (FLT3) and multi-targeted kinase inhibitor, in patients with acute myeloid leukemia and high-risk myelodysplastic syndrome with either wild-type or mutated FLT3. J Clin Oncol. 2010;28(28):4339-4345.
34. Knapper S, Burnett AK, Littlewood T, et al. A phase 2 trial of the FLT3 inhibitor lestaurtinib (CEP701) as first-line treatment for older patients with acute myeloid leukemia not considered fit for intensive chemotherapy. Blood. 2006;108(10):3262-3270.
35. Levis M, Ravandi F, Wang ES, et al. Results from a randomized trial of salvage chemotherapy followed by lestaurtinib for patients with FLT3 mutant AML in first relapse. Blood. 2011;117(12):3294-3301.
36. Ghielmini M, Vitolo U, Kimby E, et al; Panel Members of the 1st ESMO Consensus Conference on Malignant Lymphoma. ESMO Guidelines consensus conference on malignant lymphoma 2011 part 1: diffuse large B-cell lymphoma (DLBCL), follicular lym-phoma (FL) and chronic lymphocytic leukemia (CLL). Ann Oncol. 2013;24(3):561-576.
37. Dreyling M, Thieblemont C, Gallamini A, et al. ESMO Consensus conferences: guidelines on malignant lymphoma. part 2: marginal zone lymphoma, mantle cell lymphoma, peripheral T-cell lymphoma. Ann Oncol. 2013;24(4):857-877.
38. Elliott NE, Cleveland SM, Grann V Janik J, Waldmann TA, Dave UP FERM domain mutations induce gain of function in JAK3 in adult T-cell leukemia/lymphoma. Blood. 2011;118(14):3911-3921.
39. Koskela HL, Eldfors S, Ellonen P, et al. Somatic STAT3 mutations in large granular lymphocytic leukemia. N Engl J Med. 2012;366(20): 1905-1913.
40. Alas S, Bonavida B. Inhibition of constitutive STAT3 activity sensitizes resistant non-Hodgkin's lymphoma and multiple myeloma to chemo-therapeutic drug-mediated apoptosis. Clin Cancer Res. 2003;9(1): 316-326.
41. Kim BH, Yin CH, Guo Q, et al. A small-molecule compound identified through a cell-based screening inhibits JAK/STAT pathway signaling in human cancer cells. Mol Cancer Ther. 2008;7(9): 2672-2680.
42. Diaz T, Navarro A, Ferrer G, et al. Lestaurtinib inhibition of the Jak/ STAT signaling pathway in hodgkin lymphoma inhibits proliferation and induces apoptosis. PLoS ONE. 2011;6(4):e18856.
43. Hexner EO, Serdikoff C, Jan M, et al. Lestaurtinib (CEP701) is a JAK2 inhibitor that suppresses JAK2/STAT5 signaling and the proliferation of primary erythroid cells from patients with myeloproliferative disorders. Blood. 2008;111(12):5663-5671.
44. Derenzini E, Lemoine M, Buglio D, et al. The JAK inhibitor AZD1480 regulates proliferation and immunity in Hodgkin lymphoma. Blood Cancer J. 2011;1(12):e46.
45. Hart S, Goh KC, Novotny-Diermayr V, et al. SB1518, a novel macrocyclic pyrimidine-based JAK2 inhibitor for the treatment of myeloid and lymphoid malignancies. Leukemia. 2011;25(11):1751-1759.
46. Goh KC, Ong WC, Hu C, et al. SB1518: a potent and orally active JAK2 inhibitor for the treatment of myeloproliferative disorders. Blood. 2007;110(Abstract):538.
47. Verstovsek S, Kantaijian H, Mesa RA, et al. Safety and efficacy of INCB018424, a JAK1 and JAK2 inhibitor, in myelofibrosis. N Engl J Med. 2010; 363(12): 1117-1127.
48. Santos FP, Kantarjian HM, Jain N, et al. Phase 2 study of CEP-701, an orally available JAK2 inhibitor, in patients with primary or post-polycythemia vera/essential thrombocythemia myelofibrosis. Blood. 2010; 115(6): 1131-1136.
49. Weisberg E, Liu Q, Nelson E, et al. Using combination therapy to override stromal-mediated chemoresistance in mutant FLT3-positive AML: synergism between FLT3 inhibitors, dasatinib/multi-targeted inhibitors and JAK inhibitors. Leukemia. 2012; 26(10): 2233-2244.
50. William AD, Lee AC, Blanchard S, et al. Discovery of the mac-rocycle 11-(2-pyrrolidin-1-yl-ethoxy)-14,19-dioxa-5,7,26-triaza-tetracyclo[19.3.1.1(2,6).1(8,12)]heptacosa-1(25),2(26),3,5,8,10,12(27), 16,21,23-decaene (SB1518), a potent Janus kinase 2/fms-like tyrosine kinase-3 (JAK2/FLT3) inhibitor for the treatment of myelofibrosis and lymphoma. J Med Chem. 2011; 54(13): 4638-t658.
51. Novotny-Diermayr V, Hart S, Goh KC, et al. The oral HDAC inhibitor pracinostat (SB939) is efficacious and synergistic with the JAK2 inhibitor pacritinib (SB1518) in preclinical models of AML. Blood Cancer J. 2012; 2(5): e69.
52. Verstovsek S, Machida C, Dean JP, Myint H. Pacritinib. Inhibitor of tyrosine-protein kinase JAK2, inhibitor of FLT-3, treatment of myelofibrosis. Drugs Future. 2013; 38(6): 375.
53. Verstovsek S, Odenike O, Scott B, et al. Phase I dose-escalation trial of SB1518, a novel JAK2/FLT3 inhibitor, in acute and chronic myeloid diseases, including primary or post-essential thrombocythemia/polycythemia vera myelofibrosis. Blood. 2009; 114(Abstract): 3905.
54. Younes A, Romaguera J, Fanale M, et al. Phase I study of a novel oral Janus kinase 2 inhibitor, SB1518, in patients with relapsed lymphoma: evidence of clinical and biologic activity in multiple lymphoma subtypes. J Clin Oncol. 2012; 30(33): 4161-4167.
55. Verstovsek S, Deeg HJ, Odenike O, et al. Phase 1/2 study of SB1518, a novel JAK2/FLT3 inhibitor, in the treatment of primary myelofibrosis. Blood. 2010;116(Abstract):3082.
56. Derenzini E, Younes A. Targeting the JAK-STAT pathway in lymphoma: a focus on pacritinib. Expert Opin Investig Drugs. 2013; 22(6): 775-785.
57. Cheson BD, Pfistner B, Juweid ME, et al; International Harmonization Project on Lymphoma. Revised response criteria for malignant lymphoma. J Clin Oncol. 2007; 25(5): 579-586.