Emerging treatments for thrombocytopenia: Increasing platelet production

Drug Discovery Today

Volumn 13, Issue 17-18, 2008, Pages 798-806

  Peeters, Karen ^a   Stassen, Jean Marie ^b   Collen, Désiré ^a,b   Van Geet, Chris ^a,c   Freson, Kathleen ^a  

^a UNIVERSITY OF LEUVEN   (Belgium)

^b ThromboGenics NV   (Belgium)

^c UNIVERSITY OF LEUVEN   (Belgium)

Author keywords

[No Author keywords available]

Indexed keywords

AKR 501; AUTOANTIBODY; ELTROMBOPAG; FAB 59; FLUOROURACIL; GW 395058; HYPOPHYSIS ADENYLATE CYCLASE ACTIVATING POLYPEPTIDE; INTERFERON; JTZ 132; LGD 4665; MA01G4344; MACROGOL; MEGAKARYOCYTE GROWTH AND DEVELOPMENT FACTOR; NEUTRALIZING ANTIBODY; NIP 004; NPLATE; PRTX 100; RECOMBINANT INTERLEUKIN 11; RECOMBINANT THROMBOPOIETIN; REMIPLISTIM; RWJ 800088; SB 559448; THROMBOCYTE FACTOR 4; THROMBOPOIETIN; TRANSCRIPTION FACTOR GATA 1; TRANSCRIPTION FACTOR RUNX1; UNCLASSIFIED DRUG; YM 477;

ANAPHYLAXIS; CLINICAL TRIAL; CROSS REACTION; DISEASE SEVERITY; DRUG DOSE COMPARISON; DRUG EFFICACY; DRUG INDICATION; DRUG MECHANISM; DRUG SAFETY; DRUG TOLERABILITY; FLUID RETENTION; HUMAN; MEGAKARYOPOIESIS; NONHUMAN; REVIEW; SIDE EFFECT; SINGLE DRUG DOSE; THROMBOCYTOPENIA; THROMBOCYTOPOIESIS; TREATMENT RESPONSE;

ANIMALS; BLOOD PLATELETS; CELL PROLIFERATION; HUMANS; MEGAKARYOCYTES; PLATELET-DERIVED GROWTH FACTOR; THROMBOCYTOPENIA;

EID: 51249100441     PISSN: 13596446     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.drudis.2008.06.002     Document Type: Review

References (90)

1. Kaushansky K. The thrombocytopenia of cancer. Prospects for effective cytokine therapy. Hematol. Oncol. Clin. North Am. 10 (1996) 431-455
2. Ballem P.J., et al. Kinetic studies of the mechanism of thrombocytopenia in patients with human immunodeficiency virus infection. N. Engl. J. Med. 327 (1992) 1779-1784
3. Mittelman M., and Zeidman A. Platelet function in the myelodysplastic syndromes. Int. J. Hematol. 71 (2000) 95-98
4. Lazarus A.H., et al. Comparison of platelet immunity in patients with SLE and with ITP. Transfus. Sci. 22 (2000) 19-27
5. Lawrence S.P., et al. Course of thrombocytopenia of chronic liver disease after transjugular intrahepatic portosystemic shunts (TIPS). A retrospective analysis. Dig. Dis. Sci. 40 (1995) 1575-1580
6. Surgenor D.M., et al. Collection and transfusion of blood in the United States, 1982-1988. N. Engl. J. Med. 322 (1990) 1646-1651
7. Wallace E.L., et al. Collection and transfusion of blood and blood components in the United States, 1992. Transfusion 35 (1995) 802-812
8. Williams N., and Levine R.F. The origin, development and regulation of megakaryocytes. Br. J. Haematol. 52 (1982) 173-180
9. Radley J.M., and Scurfield G. The mechanism of platelet release. Blood 56 (1980) 996-999
10. Choi E.S., et al. Platelets generated in vitro from proplatelet-displaying human megakaryocytes are functional. Blood 85 (1995) 402-413
11. Junt T., et al. Dynamic visualization of thrombopoiesis within bone marrow. Science 317 (2007) 1767-1770
12. Kuter D.J., et al. The purification of megapoietin: a physiological regulator of megakaryocyte growth and platelet production. Proc. Natl. Acad. Sci. U.S.A. 91 (1994) 11104-11108
13. de Sauvage F.J., et al. Stimulation of megakaryocytopoiesis and thrombopoiesis by the c-Mpl ligand. Nature 369 (1994) 533-538
14. Sohma Y., et al. Molecular cloning and chromosomal localization of the human thrombopoietin gene. FEBS Lett. 353 (1994) 57-61
15. Methia N., et al. Oligodeoxynucleotides antisense to the proto-oncogene c-mpl specifically inhibit in vitro megakaryocytopoiesis. Blood 82 (1993) 1395-1401
16. Debili N., et al. The Mpl receptor is expressed in the megakaryocytic lineage from late progenitors to platelets. Blood 85 (1995) 391-401
17. Gurney A.L., et al. Thrombocytopenia in c-mpl-deficient mice. Science 265 (1994) 1445-1447
18. Ballmaier M., et al. c-mpl mutations are the cause of congenital amegakaryocytic thrombocytopenia. Blood 97 (2001) 139-146
19. Nichol J.L., et al. Megakaryocyte growth and development factor. Analyses of in vitro effects on human megakaryopoiesis and endogenous serum levels during chemotherapy-induced thrombocytopenia. J. Clin. Invest. 95 (1995) 2973-2978
20. Hou M., et al. Plasma thrombopoietin levels in thrombocytopenic states: implication for a regulatory role of bone marrow megakaryocytes. Br. J. Haematol. 101 (1998) 420-424
21. Kuter D.J., and Rosenberg R.D. The reciprocal relationship of thrombopoietin (c-Mpl ligand) to changes in the platelet mass during busulfan-induced thrombocytopenia in the rabbit. Blood 85 (1995) 2720-2730
22. Sungaran R., et al. Localization and regulation of thrombopoietin mRNa expression in human kidney, liver, bone marrow, and spleen using in situ hybridization. Blood 89 (1997) 101-107
23. Kobayashi M., et al. Thrombopoietin supports proliferation of human primitive hematopoietic cells in synergy with steel factor and/or interleukin-3. Blood 88 (1996) 429-436
24. Ramsfjell V., et al. Thrombopoietin, but not erythropoietin, directly stimulates multilineage growth of primitive murine bone marrow progenitor cells in synergy with early acting cytokines: distinct interactions with the ligands for c-kit and FLT3. Blood 88 (1996) 4481-4492
25. Choi E.S., et al. The role of megakaryocyte growth and development factor in terminal stages of thrombopoiesis. Br. J. Haematol. 95 (1996) 227-233
26. Kojima H., et al. Modulation of platelet activation in vitro by thrombopoietin. Thromb. Haemost. 74 (1995) 1541-1545
27. Weich N.S., et al. Recombinant human interleukin-11 synergizes with steel factor and interleukin-3 to promote directly the early stages of murine megakaryocyte development in vitro. Blood 95 (2000) 503-509
28. Broudy V.C., et al. Thrombopoietin (c-mpl ligand) acts synergistically with erythropoietin, stem cell factor, and interleukin-11 to enhance murine megakaryocyte colony growth and increases megakaryocyte ploidy in vitro. Blood 85 (1995) 1719-1726
29. Schulze H., and Shivdasani R.A. Mechanisms of thrombopoiesis. J. Thromb. Haemost. 3 (2005) 1717-1724
30. Majka M., et al. Stromal-derived factor 1 and thrombopoietin regulate distinct aspects of human megakaryopoiesis. Blood 96 (2000) 4142-4151
31. Shivdasani R.A., and Orkin S.H. The transcriptional control of hematopoiesis. Blood 87 (1996) 4025-4039
32. Orkin S.H., et al. Transcription factor GATA-1 in megakaryocyte development. Stem Cells 16 Suppl. 2 (1998) 79-83
33. Vyas P., et al. Consequences of GATA-1 deficiency in megakaryocytes and platelets. Blood 93 (1999) 2867-2875
34. Chang A.N., et al. GATA-factor dependence of the multitype zinc-finger protein FOG-1 for its essential role in megakaryopoiesis. Proc. Natl. Acad. Sci. U.S.A. 99 (2002) 9237-9242
35. Szalai G., et al. Molecular mechanisms of megakaryopoiesis. Cell Mol. Life Sci. 63 (2006) 2460-2476
36. Li J., et al. Thrombocytopenia caused by the development of antibodies to thrombopoietin. Blood 98 (2001) 3241-3248
37. Kuter D.J., and Begley C.G. Recombinant human thrombopoietin: basic biology and evaluation of clinical studies. Blood 100 (2002) 3457-3469
38. Basser R.L., et al. Development of pancytopenia with neutralizing antibodies to thrombopoietin after multicycle chemotherapy supported by megakaryocyte growth and development factor. Blood 99 (2002) 2599-2602
39. Cwirla S.E., et al. Peptide agonist of the thrombopoietin receptor as potent as the natural cytokine. Science 276 (1997) 1696-1699
40. de Serres M., et al. Immunogenicity of thrombopoietin mimetic peptide GW395058 in BALB/c mice and New Zealand white rabbits: evaluation of the potential for thrombopoietin neutralizing antibody production in man. Stem Cells 17 (1999) 203-209
41. Frederickson S., et al. A rationally designed agonist antibody fragment that functionally mimics thrombopoietin. Proc. Natl. Acad. Sci. U.S.A. 103 (2006) 14307-14312
42. Wang B., et al. Pharmacodynamics and pharmacokinetics of AMG 531, a novel thrombopoietin receptor ligand. Clin. Pharmacol. Ther. 76 (2004) 628-638
43. Broudy V.C., and Lin N.L. AMG531 stimulates megakaryopoiesis in vitro by binding to Mpl. Cytokine 25 (2004) 52-60
44. Hartley C., et al. The novel thrombopoietic agent AMG 531 is effective in pre-clinical models of chemo/radiotherapy induced thrombocytopenia. Proc. Am. Assn. Cancer Res. 46 (2005) (abstract 1233)
45. Bussel J.B., et al. AMG, 531 a thrombopoiesis-stimulating protein, for chronic ITP. N. Engl. J. Med. 355 (2006) 1672-1681
46. Kuter D.J., et al. Efficacy of romiplostim in patients with chronic immune thrombocytopenic purpura: a double-blind randomised controlled trial. Lancet 371 (2008) 395-403
47. Newland A., et al. An open-label, unit dose-finding study of AMG 531, a novel thrombopoiesis-stimulating peptibody, in patients with immune thrombocytopenic purpura. Br. J. Haematol. 135 (2006) 547-553
48. Liem-Moolenaar, M. et al. Pharmacodynamics and pharmacokinetics of the novel thrombopoietin mimetic peptide RWJ-800088 in humans. Clin. Pharmacol. Ther., online publication 21 May 2008
49. Kakkar A.K. An expanding role for antithrombotic therapy in cancer patients. Cancer Treat. Rev. 29 Suppl. 2 (2003) 23-26
50. Jenkins J.M., et al. Phase 1 clinical study of eltrombopag, an oral, nonpeptide thrombopoietin receptor agonist. Blood 109 (2007) 4739-4741
51. Bussel J.B., et al. Eltrombopag for the treatment of chronic idiopathic thrombocytopenic purpura. N. Engl. J. Med. 357 (2007) 2237-2247
52. McHutchison J.G., et al. Eltrombopag for thrombocytopenia in patients with cirrhosis associated with hepatitis C. N. Engl. J. Med. 357 (2007) 2227-2236
53. Cacoub P., et al. Extrahepatic manifestations associated with hepatitis C virus infection. A prospective multicenter study of 321 patients. The GERMIVIC. Groupe d'Etude et de Recherche en Medecine Interne et Maladies Infectieuses sur le Virus de l'Hepatite C. Medicine (Baltimore) 79 (2000) 47-56
54. Wang C.S., et al. Strong association of hepatitis C virus (HCV) infection and thrombocytopenia: implications from a survey of a community with hyperendemic HCV infection. Clin. Infect. Dis. 39 (2004) 790-796
55. Erickson-Miller C.L., et al. Species specificity and receptor domain interaction of a small TPO receptor agonist. Blood 104 (2004) (abstract 2909)
56. Erickson-Miller C.L., et al. Discovery and characterization of a selective, nonpeptidyl thrombopoietin receptor agonist. Exp. Hematol. 33 (2005) 85-93
57. Suzuki K., et al. YM477, a novel orally-active thrombopoietin receptor agonist. Blood 106 (2005) (abstract 2298)
58. Desjardins R.E., et al. Single and multiple oral doses of AKR-501 (TM477) increase the platelet count in healthy volunteers. Blood 106 (2006) (abstract 477)
59. Dziewanowska Z.E., et al. Single and multiple oral doses of LGD-4665, a small molecule thrombopoietin receptor agonist, increase platelet counts in healthy male subjects. Blood 110 (2007) (abstract 1298)
60. Su S.-F., et al. A phase I study to investigate the pharmacokinetics (PK) and pharmacodynamics (PD) of an oral platelet growth factor (SB-559448) in healthy subjects. Blood 108 (2006) (abstract 1072)
61. Inagaki K., et al. Induction of megakaryocytopoiesis and thrombocytopoiesis by JTZ-132, a novel small molecule with thrombopoietin mimetic activities. Blood 104 (2004) 58-64
62. Nakamura T., et al. A novel nonpeptidyl human c-Mpl activator stimulates human megakaryopoiesis and thrombopoiesis. Blood 107 (2006) 4300-4307
63. Orita T., et al. A novel therapeutic approach for thrombocytopenia by minibody agonist of the thrombopoietin receptor. Blood 105 (2005) 562-566
64. Kai M., et al. Switching constant domains enhances agonist activities of antibodies to a thrombopoietin receptor. Nat. Biotechnol. 26 (2008) 209-211
65. Roux K.H., et al. Flexibility of human IgG subclasses. J. Immunol. 159 (1997) 3372-3382
66. Musashi M., et al. Direct and synergistic effects of interleukin 11 on murine hemopoiesis in culture. Proc. Natl. Acad. Sci. U.S.A. 88 (1991) 765-769
67. Hirayama F., et al. Clonal proliferation of murine lymphohemopoietic progenitors in culture. Proc. Natl. Acad. Sci. U.S.A. 89 (1992) 5907-5911
68. Teramura M., et al. Interleukin-11 enhances human megakaryocytopoiesis in vitro. Blood 79 (1992) 327-331
69. Bruno E., et al. Effects of recombinant interleukin 11 on human megakaryocyte progenitor cells. Exp. Hematol. 19 (1991) 378-381
70. Du X., and Williams D.A. Interleukin-11: review of molecular, cell biology, and clinical use. Blood 89 (1997) 3897-3908
71. Neben S., et al. Synergistic effects of interleukin-11 with other growth factors on the expansion of murine hematopoietic progenitors and maintenance of stem cells in liquid culture. Exp. Hematol. 22 (1994) 353-359
72. Goldman S., et al. Recombinant human interleukin-11 (rhIL-11) stimulates megakaryocyte maturation and increase in peripheral platelet number in vivo. Blood 78 (1991) (518A)
73. Tepler I., et al. A randomized placebo-controlled trial of recombinant human interleukin-11 in cancer patients with severe thrombocytopenia due to chemotherapy. Blood 87 (1996) 3607-3614
74. Gordon M.S., et al. A phase I trial of recombinant human interleukin-11 (neumega rhIL-11 growth factor) in women with breast cancer receiving chemotherapy. Blood 87 (1996) 3615-3624
75. Isaacs C., et al. Randomized placebo-controlled study of recombinant human interleukin-11 to prevent chemotherapy-induced thrombocytopenia in patients with breast cancer receiving dose-intensive cyclophosphamide and doxorubicin. J. Clin. Oncol. 15 (1997) 3368-3377
76. Cripe L.D., et al. Phase II trial of subcutaneous recombinant human interleukin 11 with subcutaneous recombinant human granulocyte-macrophage colony stimulating factor in patients with acute myeloid leukemia (AML) receiving high-dose cytarabine during induction: ECOG 3997. Leuk. Res. 30 (2006) 823-827
77. Mitus A.J., et al. Improved survival for patients with acute myelogenous leukemia. J. Clin. Oncol. 13 (1995) 560-569
78. Kurzrock R., et al. Pilot study of low-dose interleukin-11 in patients with bone marrow failure. J. Clin. Oncol. 19 (2001) 4165-4172
79. Ghalib R., et al. Recombinant human interleukin-11 improves thrombocytopenia in patients with cirrhosis. Hepatology 37 (2003) 1165-1171
80. Artz A.S., et al. Interleukin-11 for thrombocytopenia associated with hepatitis C. J. Clin. Gastroenterol. 33 (2001) 425-426
81. Ustun C., et al. Interleukin-11 administration normalizes the platelet count in a hypersplenic cirrhotic patient. Ann. Hematol. 81 (2002) 609-610
82. Yatko C., et al. PRTX-100 inhibits platelet phagocytosis in vitro. Blood 108 (2006) (abstract 1081)
83. Lambert M.P., et al. Platelet factor 4 is a negative autocrine in vivo regulator of megakaryopoiesis: clinical and therapeutic implications. Blood 110 (2007) 1153-1160
84. Freson K., et al. PACAP and its receptor VPAC1 regulate megakaryocyte maturation: therapeutic implications. Blood 111 (2008) 1885-1893
85. Briquet-Laugier V., et al. Probing platelet factor 4 alpha-granule targeting. J. Thromb. Haemost. 2 (2004) 2231-2240
86. Sato Y., et al. Carboxyl-terminal heparin-binding fragments of platelet factor 4 retain the blocking effect on the receptor binding of basic fibroblast growth factor. Jpn. J. Cancer Res. 84 (1993) 485-488
87. Freson K., et al. The pituitary adenylate cyclase-activating polypeptide is a physiological inhibitor of platelet activation. J. Clin. Invest. 113 (2004) 905-912
88. Archimbaud E., et al. A randomized, double-blind, placebo-controlled study with pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) as an adjunct to chemotherapy for adults with de novo acute myeloid leukemia. Blood 94 (1999) 3694-3701
89. Bolwell B., et al. Phase 1 study of pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) in breast cancer patients after autologous peripheral blood progenitor cell (PBPC) transplantation. Bone Marrow Transplant. 26 (2000) 141-145
90. Freson K., et al. Different substitutions at residue D218 of the X-linked transcription factor GATA1 lead to altered clinical severity of macrothrombocytopenia and anemia and are associated with variable skewed X inactivation. Hum. Mol. Genet. 11 (2002) 147-152