Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Manuscript
  • Published:

MDS

Colony-forming unit-megakaryocyte (CFU-meg) numbers and serum thrombopoietin concentrations in thrombocytopenic disorders: an inverse correlation in myelodysplastic syndromes

Abstract

We studied both serum-free colony-forming unit-megakaryocyte (CFU-meg) numbers and serum thrombopoietin (TPO) levels in 14 patients with aplastic anemia (AA), 37 patients with myelodysplastic syndromes (MDS) and 23 patients with idiopathic thrombocytopenic purpura (ITP) to assess thrombopoiesis in these thrombocytopenic disorders. The mean CFU-meg numbers were lower in AA and MDS patients (10.7 ± 11.4 and 42.3 ± 58.5/105 BMLD cells) than in healthy controls (103.1 ± 57.3/105 BMLD cells) (P < 0.0001 and P = 0.0053, respectively), although they were distributed variably in MDS. ITP patients showed higher CFU-meg numbers (223.2 ± 143.5/105 BMLD cells) (P = 0.017). The mean TPO concentrations were higher in both AA (986.8 ± 500.8 pg/ml) and MDS patients (838.2 ± 639.1 pg/ml) than in healthy controls (80.7 ± 38.8 pg/ml) (P < 0.0001), although they were distributed from high to low in MDS. ITP patients showed a slight elevation of TPO (123.1 ± 55.3 pg/ml) P = 0.0106). The TPO levels was inversely correlated to both platelet counts and CFU-meg numbers (correlative coefficient (CC): −0.719 and −0.682, P < 0.0001) in AA, but not in ITP. In MDS, the inverse correlation to TPO was stronger in CFU-meg (CC: −0.678, P < 0.0001) than in platelet counts (CC: −0.538, P = 0.0014), suggesting that CFU-meg plays an important role in regulating TPO production in this heterogenous disorder. CFU-meg and TPO may provide useful information for understanding thrombopoiesis of MDS, especially for application of TPO.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3

Similar content being viewed by others

References

  1. Vainchenker W, Guichard J, Breton-Gorius J . Growth of human megakaryocyte colonies in culture from fetal, neonatal, and adult peripheral blood cells: ultrastructural analysis Blood Cells 1979 5: 25–42

    CAS  PubMed  Google Scholar 

  2. Hoffman R, Mazur E, Bruno E, Floyd V . Assay of an activity in the serum of patients with disorders of thrombopoiesis that stimulates formation of megakaryocytic colonies New Engl J Med 1981 305: 533–538

    Article  CAS  Google Scholar 

  3. Messner HA, Jamal N, Izaguirre C . The growth of large megakaryocyte colonies from human bone marrow J Cell Physiol 1982 : (Suppl. 1) 45–51

  4. Debili N, Wendling F, Cosman D, Titeux M, Florindo C, Dusanter-Fourt I, Schooley K, Methia N, Charon M, Nador R, Bettaieb A, Vainchenker W . The Mpl receptor is expressed in the megakaryocytic lineage from late progenitors to platelets Blood 1995 85: 391–401

    CAS  PubMed  Google Scholar 

  5. Lok S, Kaushansky K, Holly RD, Kuijper JL, Lofton-Day CE, Oort PJ, Grant FJ, Helpel MD, Burkhead SK, Kramer JM, Bell LA, Sprecher CA, Blumberg H, Johnson R, Prunkard D, Ching AFT, Mathewes SL, Bailey MC, Forstrom JW, Buddle MM, Osborn SG, Evans SJ, Sheppard PO, Presnell SR, O'Hara PJ, Hagen FS, Roth GJ, Foster DC . Cloning and expression of murine thrombopoietin cDNA and stimulation of platelet production in vivo Nature 1994 369: 565–568

    Article  CAS  Google Scholar 

  6. Kuter DJ, Beeler DL, Rosenberg RD . The purification of megapoietin: a physiological regulator of megakaryocyte growth and platelet production Proc Natl Acad Sci USA 1994 91: 11104–11108

    Article  CAS  Google Scholar 

  7. Kuter DJ, Rosenberg RD . Appearance of a megakaryocyte growth-promoting activity, megalopoietin, during acute thrombocytopenia in the rabbit Blood 1994 84: 1464–1472

    CAS  PubMed  Google Scholar 

  8. Kuter DJ, Rosenberg RD . The reciprocal relationship of thrombopoietin (c-Mpl ligand) to changes in the platelet mass during busulfan-induced thrombocytopenia in the rabbit Blood 1995 85: 2720–2730

    CAS  PubMed  Google Scholar 

  9. Ulich TR, del Castillo J, Yin S, Swift S, Padilla D, Senaldi G, Bennett L, Shutter J, Bogenberger J, Sun D, Samal B, Shimamoto G, Lee R, Steinbrink R, Boone T, Sheridan WT, Hunt P . Megakaryocyte growth and development factor ameliorates carboplatin-induced thrombocytopenia in mice Blood 1995 86: 971–976

    CAS  PubMed  Google Scholar 

  10. Stoffel R, Wiestner A, Skoda RC . Thrombopoietin in thrombocytopenic mice: evidence against regulation at the mRNA level and for a direct regulatory role of platelets Blood 1996 87: 567–574

    CAS  PubMed  Google Scholar 

  11. McCarty JM, Sprugel KH, Fox NE, Sabath DE, Kaushansky K . Murine thrombopoietin mRNA levels are modulated by platelet count Blood 1995 86: 3668–3675

    CAS  PubMed  Google Scholar 

  12. Kosugi S, Kurata Y, Tomiyama T, Tahara T, Kato T, Tadokoro S, Shiraga M, Honda S, Kanakura T, Matsuzawa M . Circulating thrombopoietin level in chronic immune thrombocytopenic purpura Br J Haematol 1996 93: 704–706

    Article  CAS  Google Scholar 

  13. Emmons RVB, Reid DM, Cohen RL, Meng G, Young NS, Dunbar CE, Shulman NR . Human thrombopoietin levels are high when thrombocytopenia is due to megakaryocyte deficiency and low when due to increased platelet destruction Blood 1996 87: 4068–4071

    CAS  Google Scholar 

  14. Kuefer MU, Wang WC, Head DR, Wilimas JA, Furman WL, Liu Q, Hornkohl AC, Best DM, Jackson CW . Thrombopoietin level in young patients is related to megakaryocyte frequency and platelet count J Pediatr Hematol Oncol 1998 20: 36–43

    Article  CAS  Google Scholar 

  15. Hou M, Andersson PO, Stockelberg D, Mellqvist UH, Ridell B, Wadenvik H . Plasma thrombopoietin levels in thrombocytopenic states: implication for a regulatory role of bone marrow megakaryocytes Br J Haematol 1998 101: 420–424

    Article  CAS  Google Scholar 

  16. Bennett JM, Catovsky D, Daniel MT, Flandrin G, Galton DA, Gralnick HR, Sultan C . Proposals for the classification of the myelodysplastic syndromes Br J Haematol 1982 51: 189–199

    Article  CAS  Google Scholar 

  17. Dan K, Gomi S, Nomura T . Kinetics of megakaryocyte progenitor cells in idiopathic thrombocytopenic purpura Blut 1990 61: 303–306

    Article  CAS  Google Scholar 

  18. Dan K, An E, Futaki M, Inokuchi K, Gomi S, Yamada T, Ogata K, Tanabe Y, Ohki I, Shinohara T, Nomura T . Megakaryocyte, erythroid and granulocyte–macrophage colony formation in myelodysplastic syndromes Acta Haematol 1993 89: 113–118

    Article  CAS  Google Scholar 

  19. Abgrall JF, El-Kassar N, Berthou C, Renard I, Cauvin JM, Le Pailleur A, Autrand C, Sensebe L, Guern G, Zilliken P, Le Gall G, Briere J . In vitro megakaryocyte colony formation in patients with idiopathic thrombocytopenic purpura: differences between acute and chronic ITP Int J Cell Cloning 1992 10: 28–32

    Article  CAS  Google Scholar 

  20. Abgrall JF, Berthou C, Sensebe L, Le Niger C, Escoffre M . Decreased in vitro megakaryocyte colony formation in chronic idiopathic thrombocytopenic purpura Br J Haematol 1993 85: 803–804

    Article  CAS  Google Scholar 

  21. Sugiyama H, Yagita M, Takahashi T, Nakamura K, Iho S, Hoshino T, Imura H . Megakaryocytopoiesis in idiopathic thrombocytopenic purpura Acta Haematol Japan 1986 50: 119–128

    Google Scholar 

  22. Hiyoyama K, Wada H, Shimura M, Nakasaki T, Katayama N, Nishikawa M, Shiku H, Tahara T, Kato T . Increased serum levels of thrombopoietin in patients with thrombotic thrombocytopenic purpura, idiopathic thrombocytopenic purpura, or disseminated intravascular coagulation Blood Coagul Fibrin 1997 8: 345–349

    Article  CAS  Google Scholar 

  23. Tahara T, Usuki K, Sato H, Ohashi H, Morita H, Tsumura H, Matsumoto A, Miyazaki H, Urabe A, Kato T . A sensitive sandwich ELISA for measuring thrombopoietin in human serum: serum thrombopoietin levels in healthy volunteers and in patients with haemopoietic disorders Br J Haematol 1996 93: 783–788

    Article  CAS  Google Scholar 

  24. Ichikawa N, Ishida F, Shimodaira S, Tahara T, Kato T, Kitano K . Regulation of serum thrombopoietin levels by platelets and megakaryocytes in patients with aplastic anaemia and idiopathic thrombocytopenic purpura Thromb Haemost 1996 76: 156–160

    Article  CAS  Google Scholar 

  25. Marsh JCW, Gibson FM, Prue RL, Bowen A, Dunn VT, Hornkohl AC, Nichol JL, Gordon-Smith EC . Serum thrombopoietin levels in patients with aplastic anaemia Br J Haematol 1996 95: 605–610

    Article  CAS  Google Scholar 

  26. Hirayama Y, Sakamaki S, Matsunaga T, Kuga T, Kuroda H, Kusakabe T, Sasaki K, Fujiwara K, Kato J, Kogawa K, Koyama R, Niitsu Y . Concentrations of thrombopoietin in bone marrow in normal subjects and in patients with idiopathic thrombocytopenic purpura, aplastic anemia, and essential thrombocythemia correlate with its mRNA expression of bone marrow stromal cells Blood 1998 92: 46–52

    CAS  PubMed  Google Scholar 

  27. Schrezenmeier H, Griesshammer M, Hornkohl A, Nichol JL, Hecht T, Heimpel H, Kubanek B, Raghavachar A . Thrombopoietin serum levels in patients with aplastic anaemia: correlation with platelet count and persistent elevation in remission Br J Haematol 1998 100: 571–576

    Article  CAS  Google Scholar 

  28. Juvonen E, Partanen S, Knuutila S, Ruutu T . Colony formation by megakaryocyte progenitors in myelodysplastic syndromes Eur J Haematol 1989 42: 389–395

    Article  CAS  Google Scholar 

  29. Geissler D, Zwierzina H, Pechlaner C, Gaggl S, Schmalzl F, Konwalinka G, Braunsteiner H . Abnormal megakaryopoiesis in patients with myelodysplastic syndromes: analysis of cellular and humoral defects Br J Haematol 1989 73: 29–35

    Article  CAS  Google Scholar 

  30. Zwierzina H, Rollinger-Holzinger I, Nuessler V, Herold M, Meng YG . Endogenous serum thrombopoietin concentrations in patients with myelodysplastic syndromes Leukemia 1998 12: 59–64

    Article  CAS  Google Scholar 

  31. Tamura H, Ogata K, Luo S, Nakamura K, Yokose N, Dan K, Tohyama K, Yoshida Y, Hamaguchi H, Sakamaki H, Kuwaki T, Tahara T, Kato T, Nomura T . Plasma thrombopoietin (TPO) levels and expression of TPO receptor on platelets in patients with myelodysplastic syndromes Br J Haematol 1998 103: 778–784

    Article  CAS  Google Scholar 

  32. Shivdasani RA, Rosenblatt MF, Zucker-Franklin D, Jackson CW, Hunt P, Saris CJM, Orkin H . Transcription factor NF-E2 is required for platelet formation independent of the actions of thrombopoietion/MGDF in megakaryocyte development Cell 1995 81: 695–704

    Article  CAS  Google Scholar 

  33. Guerriero A, Worford L, Holland HK, Guo G-R, Sheehan K, Waller EK . Thrombopoietin is synthesized by bone marrow stromal cells Blood 1997 90: 444–455

    Google Scholar 

Download references

Acknowledgements

The authors are grateful to Mr Shigehiro Nakashima for his technical assistance.

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wang, W., Matsuo, T., Yoshida, S. et al. Colony-forming unit-megakaryocyte (CFU-meg) numbers and serum thrombopoietin concentrations in thrombocytopenic disorders: an inverse correlation in myelodysplastic syndromes. Leukemia 14, 1751–1756 (2000). https://doi.org/10.1038/sj.leu.2401898

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.leu.2401898

Keywords

Search

Quick links