thrombopoiesis

Summary

Summary: The process of generating thrombocytes (BLOOD PLATELETS) from the pluripotent HEMATOPOIETIC STEM CELLS in the BONE MARROW via the MEGAKARYOCYTES. The humoral factor with thrombopoiesis-stimulating activity is designated THROMBOPOIETIN.

Top Publications

  1. Barata L, Miwa T, Sato S, Kim D, Mohammed I, Song W. Deletion of Crry and DAF on murine platelets stimulates thrombopoiesis and increases factor H-dependent resistance of peripheral platelets to complement attack. J Immunol. 2013;190:2886-95 pubmed publisher
    ..Examination of Pf4-Cre(+)-Crry(flox/flox) mouse bone marrows revealed exceedingly active thrombopoiesis. Thus, under in vivo conditions, Crry/DAF deficiency on platelets led to abnormal platelet turnover, but ..
  2. Jurak Begonja A, Hoffmeister K, Hartwig J, Falet H. FlnA-null megakaryocytes prematurely release large and fragile platelets that circulate poorly. Blood. 2011;118:2285-95 pubmed publisher
    ..5- to 5-fold increase in MK numbers, indicating increased thrombopoiesis in vivo...
  3. Reems J, Pineault N, Sun S. In vitro megakaryocyte production and platelet biogenesis: state of the art. Transfus Med Rev. 2010;24:33-43 pubmed publisher
  4. Perreault S, Burzynski J. Romiplostim: a novel thrombopoiesis-stimulating agent. Am J Health Syst Pharm. 2009;66:817-24 pubmed publisher
    ..The extrapolated drug cost for weekly dosing for one year is approximately $55,250. Romiplostim is a novel thrombopoietic-stimulating agent for use in patients with chronic ITP who have not responded to other therapies. ..
  5. Nichol J. AMG 531: an investigational thrombopoiesis-stimulating peptibody. Pediatr Blood Cancer. 2006;47:723-5 pubmed
    ..A new peptibody, AMG 531, has been shown to increase platelet counts in preclinical and Phase 1 and Phase 2 studies and to be generally safe and tolerable in those studies. ..
  6. Abe Y, Wada H, Tomatsu H, Sakaguchi A, Nishioka J, Yabu Y, et al. A simple technique to determine thrombopoiesis level using immature platelet fraction (IPF). Thromb Res. 2006;118:463-9 pubmed
    ..has been measured by fully automated analyzer (XE-2100) as reticulated platelet (RP) which is reflected with thrombopoiesis in bone marrow. IPF value in the healthy volunteers was 3.3% (1.0-10...
  7. Junt T, Schulze H, Chen Z, Massberg S, Goerge T, Krueger A, et al. Dynamic visualization of thrombopoiesis within bone marrow. Science. 2007;317:1767-70 pubmed
    ..These results confirm the concept of proplatelet formation in vivo and are consistent with the possibility that blood flow-induced hydrodynamic shear stress is a biophysical determinant of thrombopoiesis.
  8. Liu C, Li J, Meng F, Liang S, Deng R, Li C, et al. Polysaccharides from the root of Angelica sinensis promotes hematopoiesis and thrombopoiesis through the PI3K/AKT pathway. BMC Complement Altern Med. 2010;10:79 pubmed publisher
  9. Zou Z, Schmaier A, Cheng L, Mericko P, Dickeson S, Stricker T, et al. Negative regulation of activated alpha-2 integrins during thrombopoiesis. Blood. 2009;113:6428-39 pubmed publisher

More Information

Publications62

  1. Tober J, McGrath K, Palis J. Primitive erythropoiesis and megakaryopoiesis in the yolk sac are independent of c-myb. Blood. 2008;111:2636-9 pubmed publisher
    ..5 yolk sac and E11.5 liver. Despite this impaired megakaryocyte potential, c-myb-null fetuses had normal platelet numbers at E12.5 but became thrombocytopenic by E15.5, suggesting that c-myb is required for sustained thrombopoiesis.
  2. Fock E, Yan F, Pan S, Chong B. NF-E2-mediated enhancement of megakaryocytic differentiation and platelet production in vitro and in vivo. Exp Hematol. 2008;36:78-92 pubmed
    ..By overexpressing the p45 subunit of NF-E2, we aim to increase the proportion of mature MKs and the potential for platelet production in vitro and in vivo...
  3. Ciurea S, Hoffman R. Cytokines for the treatment of thrombocytopenia. Semin Hematol. 2007;44:166-82 pubmed
    ..Thrombopoietin (TPO) is the physiological regulator of thrombopoiesis. Although a number of cytokines (interleukin [IL]-1, IL-3, and IL-6) were first evaluated for their ability to ..
  4. McCormack M, Hall M, Schoenwaelder S, Zhao Q, Ellis S, Prentice J, et al. A critical role for the transcription factor Scl in platelet production during stress thrombopoiesis. Blood. 2006;108:2248-56 pubmed
    ..Less is known about platelet production in the setting of stress thrombopoiesis, a pivotal event in the context of cytotoxic chemotherapy...
  5. Schulze H, Korpal M, Hurov J, Kim S, Zhang J, Cantley L, et al. Characterization of the megakaryocyte demarcation membrane system and its role in thrombopoiesis. Blood. 2006;107:3868-75 pubmed
    ..These observations collectively suggest a signaling pathway wherein PI-4,5-P(2) might facilitate DMS development and local assembly of actin fibers in preparation for platelet biogenesis. ..
  6. Anderson N, Berberovic Z, Berndl E, Bailey M, Flenniken A, Osborne L, et al. Cytopenia induction by 5-fluorouracil identifies thrombopoietic mutants in sensitized ENU mutagenesis screens. Exp Hematol. 2012;40:48-60 pubmed publisher
  7. Kerrigan S, Gaur M, Murphy R, Shattil S, Leavitt A. Caspase-12: a developmental link between G-protein-coupled receptors and integrin alphaIIbbeta3 activation. Blood. 2004;104:1327-34 pubmed
  8. O Brien J, Baglole C, Garcia Bates T, Blumberg N, Francis C, Phipps R. 15-deoxy-Delta12,14 prostaglandin J2-induced heme oxygenase-1 in megakaryocytes regulates thrombopoiesis. J Thromb Haemost. 2009;7:182-9 pubmed publisher
    ..The role of HO-1 activity in thrombopoiesis was studied using established in vitro models of platelet production...
  9. Dunois Lardé C, Capron C, Fichelson S, Bauer T, Cramer Bordé E, Baruch D. Exposure of human megakaryocytes to high shear rates accelerates platelet production. Blood. 2009;114:1875-83 pubmed publisher
    ..In conclusion, MK exposure to high shear rates promotes platelet production via GPIb, depending on microtubule assembly and elongation. ..
  10. Monzen S, Takahashi K, Yoshino H, Kasai Eguchi K, Abe Y, Maruyama A, et al. Heavy ion beam irradiation regulates the mRNA expression in megakaryocytopoiesis from human hematopoietic stem/progenitor cells. J Radiat Res. 2009;50:477-86 pubmed
    ..0-fold and a 21.8-fold increase at 6 hr in comparison to the initial control. These results showed that the heavy ion beams affect megakaryocytopoiesis/ erythropoiesis differentiation of human HSPCs on the gene expression level. ..
  11. Lin H, Traver D, Zhu H, Dooley K, Paw B, Zon L, et al. Analysis of thrombocyte development in CD41-GFP transgenic zebrafish. Blood. 2005;106:3803-10 pubmed
    ..These studies have shown that it is possible to identify thrombocytes, thrombocyte precursors, and, possibly, early hematopoietic stem cells in zebrafish embryos and track their proliferation and maturation. ..
  12. Scholz M, Gross A, Loeffler M. A biomathematical model of human thrombopoiesis under chemotherapy. J Theor Biol. 2010;264:287-300 pubmed publisher
    ..We present a simple ordinary differential equations model of thrombopoiesis under chemotherapy which maps the dynamics of stem cells, CFU-Mk, megakaryocytes and platelets in spleen and ..
  13. Schwertz H, Köster S, Kahr W, Michetti N, Kraemer B, Weitz D, et al. Anucleate platelets generate progeny. Blood. 2010;115:3801-9 pubmed publisher
    ..Because this new function of platelets occurs outside of the bone marrow milieu, it raises the possibility that thrombopoiesis continues in the bloodstream.
  14. Mazharian A, Thomas S, Dhanjal T, Buckley C, Watson S. Critical role of Src-Syk-PLC{gamma}2 signaling in megakaryocyte migration and thrombopoiesis. Blood. 2010;116:793-800 pubmed publisher
    ..This correlation also holds for mice deficient in PLCgamma2. This study identifies a model in which integrin signaling via Src family kinases and Syk kinase to PLCgamma2 is required for MK spreading, migration, and platelet formation. ..
  15. Bussel J, Kuter D, George J, McMillan R, Aledort L, Conklin G, et al. AMG 531, a thrombopoiesis-stimulating protein, for chronic ITP. N Engl J Med. 2006;355:1672-81 pubmed
    ..In a phase 1-2 study, we administered a thrombopoiesis-stimulating protein, AMG 531, to patients with ITP...
  16. Schulze H, Shivdasani R. Mechanisms of thrombopoiesis. J Thromb Haemost. 2005;3:1717-24 pubmed
    ..Finally, we summarize our own studies on cellular and molecular facets of proplatelet formation and place the findings within the context of outstanding questions about mechanisms of thrombopoiesis.
  17. Nakanishi C, Doi H, Katsura K, Satomi S. Treatment with L-valine ameliorates liver fibrosis and restores thrombopoiesis in rats exposed to carbon tetrachloride. Tohoku J Exp Med. 2010;221:151-9 pubmed
    ..2 per field, p < 0.01, respectively). Importantly, the mRNA level of thrombopoietin, a key regulator of thrombopoiesis, was significantly higher in the liver of the valine group than the control group...
  18. Nakamura T, Miyakawa Y, Miyamura A, Yamane A, Suzuki H, Ito M, et al. A novel nonpeptidyl human c-Mpl activator stimulates human megakaryopoiesis and thrombopoiesis. Blood. 2006;107:4300-7 pubmed publisher
    ..These observations indicate that NIP-004 is a novel human c-Mpl activator and induces human thrombopoiesis.
  19. Fuentes R, Wang Y, Hirsch J, Wang C, Rauova L, Worthen G, et al. Infusion of mature megakaryocytes into mice yields functional platelets. J Clin Invest. 2010;120:3917-22 pubmed publisher
    b>Thrombopoiesis, the process by which circulating platelets arise from megakaryocytes, remains incompletely understood. Prior studies suggest that megakaryocytes shed platelets in the pulmonary vasculature...
  20. Zhang L, Orban M, Lorenz M, Barocke V, Braun D, Urtz N, et al. A novel role of sphingosine 1-phosphate receptor S1pr1 in mouse thrombopoiesis. J Exp Med. 2012;209:2165-81 pubmed publisher
    ..Collectively, our findings uncover a novel function of the S1P-S1pr1 axis as master regulator of efficient thrombopoiesis and might raise new therapeutic options for patients with thrombocytopenia.
  21. Vadhan Raj S. Management of chemotherapy-induced thrombocytopenia: current status of thrombopoietic agents. Semin Hematol. 2009;46:S26-32 pubmed publisher
    ..The clinical trials of romiplostim and eltrombopag are currently ongoing to optimize their dose and schedule in ameliorating chemotherapy-induced thrombocytopenia. ..
  22. Shin J, Swift J, Spinler K, Discher D. Myosin-II inhibition and soft 2D matrix maximize multinucleation and cellular projections typical of platelet-producing megakaryocytes. Proc Natl Acad Sci U S A. 2011;108:11458-63 pubmed publisher
    ..Myosin-II thus seems a central, matrix-regulated node for MK-poiesis and platelet generation...
  23. Gaur M, Kamata T, Wang S, Moran B, Shattil S, Leavitt A. Megakaryocytes derived from human embryonic stem cells: a genetically tractable system to study megakaryocytopoiesis and integrin function. J Thromb Haemost. 2006;4:436-42 pubmed
    ..Using hESCs, we have developed a renewable source of human megakaryocytes, and a genetically tractable system for studying megakaryocytopoiesis and alpha(IIb)beta(3) signaling in the native cellular environment. ..
  24. Nishikii H, Eto K, Tamura N, Hattori K, Heissig B, Kanaji T, et al. Metalloproteinase regulation improves in vitro generation of efficacious platelets from mouse embryonic stem cells. J Exp Med. 2008;205:1917-27 pubmed publisher
    ..Thus, the regulation of metalloproteinases in culture could be useful for obtaining high-quality, efficacious ESPs as an alternative platelet source for transfusions. ..
  25. Marcucci R, Romano M. Thrombopoietin and its splicing variants: structure and functions in thrombopoiesis and beyond. Biochim Biophys Acta. 2008;1782:427-32 pubmed publisher
    ..progenitors and its expression occurs in some tumors as well as in tissues not directly related to the thrombopoiesis. In this review, we summarize the structure and functions of THPO through the published evidence on its ..
  26. Antonchuk J, Hyland C, Hilton D, Alexander W. Synergistic effects on erythropoiesis, thrombopoiesis, and stem cell competitiveness in mice deficient in thrombopoietin and steel factor receptors. Blood. 2004;104:1306-13 pubmed
    ..Thus, c-Mpl(-/-) Kit(Wv/Wv) mice reveal nonredundant and synergistic effects of Tpo and SF on primitive hematopoietic cells. ..
  27. Chen Z, Naveiras O, Balduini A, Mammoto A, Conti M, Adelstein R, et al. The May-Hegglin anomaly gene MYH9 is a negative regulator of platelet biogenesis modulated by the Rho-ROCK pathway. Blood. 2007;110:171-9 pubmed
    ..This effect occurs only in the presence of myosin-IIA and implies that myosin-IIA influences thrombopoiesis negatively...
  28. Kaushansky K. Historical review: megakaryopoiesis and thrombopoiesis. Blood. 2008;111:981-6 pubmed publisher
    The study of thrombopoiesis has evolved greatly since an era when platelets were termed "the dust of the blood," only about 100 years ago...
  29. Pick M, Perry C, Lapidot T, Guimaraes Sternberg C, Naparstek E, Deutsch V, et al. Stress-induced cholinergic signaling promotes inflammation-associated thrombopoiesis. Blood. 2006;107:3397-406 pubmed
    To study the role of the stress-induced "readthrough" acetylcholinesterase splice variant, AChE-R, in thrombopoiesis, we used transgenic mice overexpressing human AChE-R (TgR)...
  30. Nurden P, Debili N, Vainchenker W, Bobe R, Bredoux R, Corvazier E, et al. Impaired megakaryocytopoiesis in type 2B von Willebrand disease with severe thrombocytopenia. Blood. 2006;108:2587-95 pubmed
    ..Immunolocalization showed VWF not only associated with platelets, but already on the megakaryocyte surface and within internal channels. In this family, type 2B VWD is clearly associated with abnormal platelet production. ..
  31. Monzen S, Takahashi K, Yoshino H, Kasai Eguchi K, Kashiwakura I. Terminal maturation of megakaryocytes and platelet production by hematopoietic stem cells irradiated with heavy-ion beams. Radiat Res. 2011;176:8-16 pubmed
    Hematopoietic processes, especially megakaryocytopoiesis and thrombopoiesis, are highly sensitive to high-linear energy transfer (LET) radiations such as heavy-ion beams that have greater biological effects than low-LET radiation...
  32. Matsubara Y, Murata M, Ikeda Y. Culture of megakaryocytes and platelets from subcutaneous adipose tissue and a preadipocyte cell line. Methods Mol Biol. 2012;788:249-58 pubmed publisher
  33. Terasawa R, Fukushi Y, Monzen S, Miura T, Takahashi K, Yoshizawa A, et al. The promoting activity on human megakaryocytopoiesis and thrombopoiesis by liquid crystal-related compounds. Biol Pharm Bull. 2009;32:976-81 pubmed
    ..colony-stimulating factor (GM-CSF), that were used as a positive control for in vitro megakaryocytopoiesis and thrombopoiesis, resulted in a dramatic increase in the total number of cells; however, their promoting activity on in vitro ..
  34. Kaushansky K. The molecular mechanisms that control thrombopoiesis. J Clin Invest. 2005;115:3339-47 pubmed
    Our understanding of thrombopoiesis--the formation of blood platelets--has improved greatly in the last decade, with the cloning and characterization of thrombopoietin, the primary regulator of this process...
  35. Yu M, Cantor A. Megakaryopoiesis and thrombopoiesis: an update on cytokines and lineage surface markers. Methods Mol Biol. 2012;788:291-303 pubmed publisher
    ..The generation of platelets from MKs is termed thrombopoiesis. The cytokine thrombopoietin (TPO) is the major regulator of megakaryopoiesis and thrombopoiesis...
  36. Kosone T, Takagi H, Horiguchi N, Toyoda M, Sohara N, Kakizaki S, et al. Hepatocyte growth factor accelerates thrombopoiesis in transgenic mice. Lab Invest. 2007;87:284-91 pubmed
    ..However, the effect of HGF on the thrombopoietic function remains unclear. The correlation between HGF and thrombopoiesis was investigated in transgenic (TG) mice overexpressing murine HGF controlled by the murine HGF by the ..
  37. Newland A, Caulier M, Kappers Klunne M, Schipperus M, Lefrere F, Zwaginga J, 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. 2006;135:547-53 pubmed
    ..The objective of this open label, phase 1-2, multicentre trial was to evaluate the safety of AMG 531, a novel thrombopoiesis-stimulating peptibody, and its effect on platelet counts in adults with immune thrombocytopenic purpura...
  38. Kashiwakura I, Inanami O, Abe Y, Satoh K, Takahashi T, Kuwabara M. Regeneration of megakaryocytopoiesis and thrombopoiesis in vitro from X-irradiated human hematopoietic stem cells. Radiat Res. 2006;166:345-51 pubmed
    ..investigated whether X-irradiated hematopoietic stem cells can be induced to undergo megakaryocytopoiesis and thrombopoiesis in vitro using cytokine combinations that have been demonstrated to be effective for conferring increased ..
  39. Yamane A, Nakamura T, Suzuki H, Ito M, Ohnishi Y, Ikeda Y, et al. Interferon-alpha 2b-induced thrombocytopenia is caused by inhibition of platelet production but not proliferation and endomitosis in human megakaryocytes. Blood. 2008;112:542-50 pubmed publisher
    ..These results defined the pathogenesis of IFN-alpha-induced thrombocytopenia and suggested possible future clinical applications for thrombopoietin mimetics. ..
  40. Ono Y, Wang Y, Suzuki H, Okamoto S, Ikeda Y, Murata M, et al. Induction of functional platelets from mouse and human fibroblasts by p45NF-E2/Maf. Blood. 2012;120:3812-21 pubmed publisher
    ..These findings demonstrate that a combination of p45NF-E2, Maf G, and Maf K is a key determinant of both megakaryopoiesis and thrombopoiesis.
  41. Yang M, Chan G, Deng R, Ng M, Cheng S, Lau C, et al. An herbal decoction of Radix astragali and Radix angelicae sinensis promotes hematopoiesis and thrombopoiesis. J Ethnopharmacol. 2009;124:87-97 pubmed publisher
    ..However, its effects on haematopoiesis and particularly thrombopoiesis have not been studied. This study aims to examine the effects of DBT on hematopoiesis and thrombopoiesis...
  42. Battinelli E, Hartwig J, Italiano J. Delivering new insight into the biology of megakaryopoiesis and thrombopoiesis. Curr Opin Hematol. 2007;14:419-26 pubmed
    ..the latest studies of megakaryocyte development into the molecular pathways that regulate megakaryopoiesis and thrombopoiesis. Decoding the pathways of megakaryopoiesis and platelet production should help revolutionize the management of ..
  43. Takahashi K, Monzen S, Eguchi Kasai K, Abe Y, Kashiwakura I. Severe damage of human megakaryocytopoiesis and thrombopoiesis by heavy-ion beam radiation. Radiat Res. 2007;168:545-51 pubmed
    ..beams on hematopoietic stem/progenitor cells, the effects of carbon-ion beams on megakaryocytopoiesis and thrombopoiesis in CD34(+) cells derived from human placental and umbilical cord blood were investigated...
  44. Deutsch V, Tomer A. Advances in megakaryocytopoiesis and thrombopoiesis: from bench to bedside. Br J Haematol. 2013;161:778-93 pubmed publisher
    ..activates a cascade of signalling molecules, which induce transcription factors to drive MK development and thrombopoiesis. Decreased turnover rate and platelet number result in increased levels of free THPO, which induces a ..
  45. Monzen S, Tashiro E, Kashiwakura I. Megakaryocytopoiesis and thrombopoiesis in hematopoietic stem cells exposed to ionizing radiation. Radiat Res. 2011;176:716-24 pubmed
    Hematopoietic processes, especially megakaryocytopoiesis and thrombopoiesis, are highly sensitive to extracellular oxidative stresses such as ionizing radiation and chemotherapeutic agents...
  46. Lannutti B, Minear J, Blake N, Drachman J. Increased megakaryocytopoiesis in Lyn-deficient mice. Oncogene. 2006;25:3316-24 pubmed
    ..This is the first direct evidence using primary MKs from Lyn-deficient mice that confirms our prior data from cell lines that Lyn kinase is a negative regulator of TPO signaling. ..
  47. Yu I, Lin S, Huang C, Tseng H, Huang P, Shi G, et al. TXAS-deleted mice exhibit normal thrombopoiesis, defective hemostasis, and resistance to arachidonate-induced death. Blood. 2004;104:135-42 pubmed
    ..role in hemostasis and thrombosis, thromboxane A(2) synthase (TXAS) is proposed to be involved in thrombopoiesis and lymphocyte differentiation...
  48. Inagaki K, Oda T, Naka Y, Shinkai H, Komatsu N, Iwamura H. Induction of megakaryocytopoiesis and thrombocytopoiesis by JTZ-132, a novel small molecule with thrombopoietin mimetic activities. Blood. 2004;104:58-64 pubmed
    ..These data suggest that JTZ-132 is a novel stimulator of megakaryocytopoiesis and thrombocytopoiesis in vitro and in vivo with TPO mimetic activities and that it is useful for the treatment of thrombocytopenia. ..
  49. Fujimoto T, Kohata S, Suzuki H, Miyazaki H, Fujimura K. Production of functional platelets by differentiated embryonic stem (ES) cells in vitro. Blood. 2003;102:4044-51 pubmed
    ..Overexpression of the cytoplasmic domain of integrin beta3 in the ES-derived platelets prevented the activation of alphaIIbbeta3, demonstrating that this system will facilitate functional platelet studies. ..
  50. Avecilla S, Hattori K, Heissig B, Tejada R, Liao F, Shido K, et al. Chemokine-mediated interaction of hematopoietic progenitors with the bone marrow vascular niche is required for thrombopoiesis. Nat Med. 2004;10:64-71 pubmed
    ..chemokines, including stromal-derived factor-1 (SDF-1) and fibroblast growth factor-4 (FGF-4), restored thrombopoiesis in Thpo(-/-) and Mpl(-/-) mice...
  51. Skomorovski K, Harpak H, Ianovski A, Vardi M, Visser T, Hartong S, et al. New TPO treatment schedules of increased safety and efficacy: pre-clinical validation of a thrombopoiesis simulation model. Br J Haematol. 2003;123:683-91 pubmed
    ..This work was aimed at validating, in mouse and in monkey experiments, a thrombopoiesis computer-model prediction that platelet counts, similar to those obtained with accepted TPO dose scheduling, ..
  52. Kaushansky K. Thrombopoietin: a tool for understanding thrombopoiesis. J Thromb Haemost. 2003;1:1587-92 pubmed
    ..has increased substantially, and it is now appreciated that in addition to its critical role in regulating thrombopoiesis, the hormone affects multiple aspects of hematopoiesis, including playing a non-redundant role in stem cell ..
  53. Ertenli I, Kiraz S, Ozturk M, Haznedaroglu I, Celik I, Calguneri M. Pathologic thrombopoiesis of rheumatoid arthritis. Rheumatol Int. 2003;23:49-60 pubmed
    ..review focuses on the current literature and our experience regarding the dual relationships of the pathologic thrombopoiesis of RA...