J. Wang (1), Z. Yi (1), S. Wang (1), Z. Li (1)
(1) Department of Medicine, NYU Cancer Institute, New York University School of Medicine, New York, New York, USA
Thrombocytopenia is a common feature of myelodysplastic syndromes (MDS). 5-aza-2’-deoxycytidine (decitabine) has been used to treat MDS with an approximately 20% response rate in thrombocytopenia. However, the mechanism of how decitabine increases platelet count is not clear. In this study, we investigated the effect of decitabine on megakaryocyte maturation and platelet release in the mouse. The effect of decitabine on megakaryocyte maturation was studied in an in vitro megakaryocyte differentiation model utilising mouse bone marrow cells and mouse megakaryoblastic cell line L8057. Decitabine (2.5 μM) is able to induce L8057 cells to differentiate into a megakaryocyte-like polyploidy cells with positive markers of acetylcholinesterase and αIIb integrin (CD41). Higher expression of αIIb integrin was also found in primary mouse bone marrow cells and human cord blood CD34+ cells cultured with both thrombopoietin and decitabine as compared to thrombopoietin alone. In addition, we noted a 30% platelet count increase in Balb/c mice 12 hours after the injection of decitabine at a clinically relevant dose (15 mg/m2), suggesting a rapid platelet release from the spleen or bone marrow. Our data suggest that decitabine increases platelet counts by enhancing platelet release and megakaryocyte maturation.
Myelodysplastic syndromes, Thrombocytopenia, decitabine
Masahito Uemura1*, Yoshihiro Fujimura2*, Masanori Matsumoto2, Hiromichi Ishizashi2, Seiji Kato2, Tomomi Matsuyama1, Ayami Isonishi2, Masatoshi Ishikawa1, Masato Yagita4, Chie Morioka1, Hitoshi Yoshiji1, Tatsuhiro Tsujimoto1, Norio Kurumatani3, Hiroshi Fukui1
Thromb Haemost 2008 99 6: 1019-1029
Elizabeth A. Price1, Catherine P. M. Hayward2,3, Karen A. Moffat3,4, Jane C. Moore2,3, Theodore E. Warkentin2,3, James L. Zehnder1,5
Thromb Haemost 2007 98 6: 1357-1361
Susanne Holzhauer1, Ana-Gabriela Sitaru1, 2, Wolfram Ebell4, Detlev Schindler5, Helmut Hanenberg6, Johannes Wirbelauer1, Ulrich Walter2, Ralf Grossmann2,3
Thromb Haemost 2007 98 6: 1291-1297
Patients receiving oral anticoagulants should be carefully managed to minimize the risk of bleeding...
Acquired haemophilia A (AHA) is a rare but often severe bleeding disorder caused by ...
Section III " Vitamin K antagonists in heart disease: Current status and perspectives" of...