| Autor: |
Sano, Keigo, Tanaka, Hirokazu, J., Luis Espinoza, Kumode, Takahiro, Serizawa, Kentaro, Fujiwara, Ryosuke, Fukui, Ayano, Morita, Yasuyoshi, Hanamoto, Hitoshi, Matsumura, Itaru |
| Jazyk: |
angličtina |
| Rok vydání: |
2021 |
| Předmět: |
|
| Zdroj: |
ACTA MEDICA KINDAI UNIVERSITY. 46(2):43-55 |
| ISSN: |
2432-7166 |
| Popis: |
[Abstract] Background: Thrombopoietin (TPO) and its receptor, c-Mpl are essential for megakaryopoiesis. Two TPO receptor agonists (TPO-RAs),Eltrombopag (ETP) and Romiplostim (Rom), which also activate c-Mpl, thereby transmitting signals to downstream molecules, are currently used for immune thrombocytopenia purpura and aplastic anemia. Furthermore, recent clinical trials demonstrated that ETP and Rom would be useful for Myelodysplastic syndromes (MDS) patients with thrombocytopenia. Lusutrombopag (LTP) is a novel TPO-RA, which is approved for thrombocytopenia associated with liver diseases. In this study, we examined the effects of LTP on the growth and differentiation of MDS CD34+ cells as a preclinical study. Method: Effects of LTP on the proliferation, differentiation, and long-term self-renewal activities of bone marrow CD34+ cells from MDS patients were assessed with liquid cultures, CFU-megakaryocyte assays, and serial replating assays, respectively. We also analyzed the effects of LTP on cytokine secretion from cultured MDS CD34+ cells with a cytokine antibody array. Results: LTP effectively promotes the growth and differentiation of MDS CD34+ cells with comparable efficacy to that exerted on CD34+ cells from healthy controls. The megakaryopoietic potential of LTP was comparable to that exerted by ETP and TPO. LTP did not stimulate growth of CD34+ MDS/AML blasts, a concern that has been associated with ETP and Rom. Both ETP and TPO induced higher levels of FGF7 than LTP from CD34+ MDS cells. Conclusion: Although LTP and ETP revealed some different biologic activities, LTP would be as effective as ETP in promoting the growth and megakaryocytic differentiation of MDS CD34+ cells. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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