The effect of decitabine on megakaryocyte maturation and platelet release

2011 ◽  
Vol 106 (08) ◽  
pp. 337-343 ◽  
Author(s):  
Jianhui Wang ◽  
Zanhua Yi ◽  
Shiyang Wang ◽  
Zongdong Li

SummaryThrombocytopenia 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.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3507-3507
Author(s):  
Jianhui Wang ◽  
Zongdong Li

Abstract Abstract 3507 Poster Board III-444 Thrombocytopenia is frequently associated with the myelodysplastic syndromes (MDS). 5-aza-2'-deoxycytidine (Decitabine) has been used to treat MDS with an approximately 20% response rate in thrombocytopenia. In this study, we have investigated the effect of Decitabine on platelet count in mouse. We report here that enhanced platelet release and maturation of megakaryocyte are two mechanisms involved in Decitabine induced elevation of platelet count. We first noted that a 30% of platelet count increase was found in the Balb/c mice 12 hours after the injection of Dectiabine at a clinically relevant dose (15 mg/m2) suggesting an instant platelet release from spleen or from megkaryocyte of bone marrow. The effect of Decitabine on megakaryocyte maturation was studied in in vitro differentiation of mouse bone marrow cells and megakaryoblastic cell line L8057. Decitabine (2.5 mm) is able to induce L8057 cells to differentiate into a megakaryocyte like polyploidy cells with positive marker of acetylcholinesterase and αIIb integrin. High expression of αIIb integrin was also found in the primary bone marrow cells cultured with both thrombopoietin and Decitabine as compared to thrombopoietin alone. The demethylation-induced transcription of GP6 has been reported in thrombopoietin induced megakaryocyte differentiation. Since Decitabine is a DNA demethylation reagent, we have investigated the GP6 expression in Decitabine treated L8057 cells and have found upregualtion of GP6 expression. Although the role of DNA demethylation in megkaryoctye differentiation still needs to be verified, our current data support that Decitabine is able to drive magakaryocyte maturation. Disclosures: No relevant conflicts of interest to declare.


1994 ◽  
Vol 29 (3) ◽  
pp. 631-634 ◽  
Author(s):  
Masako Nose ◽  
Yoshiro Aoki ◽  
Yoshiko Kawase ◽  
Gen Suzuki ◽  
Makoto Akashi ◽  
...  

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