The non-peptide thrombopoietin receptor agonist eltrombopag stimulates megakaryopoiesis in bone marrow cells from patients with relapsed multiple myeloma.
The non-peptide thrombopoietin receptor agonist eltrombopag stimulates megakaryopoiesis in bone marrow cells from patients with relapsed multiple myeloma.
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DOI：
10.1186/s13045-015-0136-2
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发表时间：
2015-04-16
影响因子：
28.5
通讯作者：
Vanasse GJ
中科院分区：
文献类型：
--
作者：
Jeong JY;Levine MS;Abayasekara N;Berliner N;Laubach J;Vanasse GJ
血小板减少是复发或难治性多发性骨髓瘤患者的一个重要问题，这促使患者需要支持性血小板输注，并需要减少化疗剂量。Eltrombopg是一种非肽、小分子血小板生成素(TPO)受体激动剂，类似于内源性人类TPO促进巨核细胞生成，可能是治疗此类患者血小板减少症的有效药物。我们检测了紫草对多发性骨髓瘤患者CD34+细胞巨核细胞集落形成能力的影响，并观察了其对原代CD138+人骨髓瘤细胞和骨髓瘤细胞系增殖、活力和凋亡的影响。单用或与促红细胞生成素和粒细胞集落刺激因子联合使用时，0.1%至100%μM对复发性疾病患者的CD138+多发性骨髓瘤细胞或骨髓瘤细胞系的原代人CD138+多发性骨髓瘤细胞的增殖没有促进作用，也没有改变硼替佐米和来那度胺暴露的人骨髓瘤细胞的细胞活力和凋亡。ELTROMBOPE通过激活Akt信号通路，刺激正常人和复发性多发性骨髓瘤患者的CD34+细胞产生巨核细胞。这些结果为未来临床研究的设计提供了原则上的证据，这些临床研究旨在检查eltrombopg治疗晚期多发性骨髓瘤患者的血小板减少症。
Thrombocytopenia is a significant problem in patients with relapsed or refractory multiple myeloma, precipitating a need for supportive platelet transfusions and necessitating decreases in delivered doses of chemotherapy. Eltrombopag is a non-peptide, small molecule thrombopoietin (TPO) receptor agonist that promotes megakaryopoiesis similar to endogenous human TPO and may be an effective agent for thrombocytopenia in this patient population. We examined the effects of eltrombopag on megakaryocyte colony-forming capacity in CD34+ cells in patients with multiple myeloma and investigated its impact on proliferation, viability, and apoptosis in primary CD138+ human myeloma cells and myeloma cell lines. Eltrombopag at doses of 0.1 to 100 μM did not enhance proliferation of primary human CD138+ multiple myeloma cells from patients with relapsed disease or myeloma cell lines when used alone or in combination with erythropoietin (EPO) and granulocyte colony-stimulating factor (G-CSF) and did not alter cell viability nor apoptosis of human myeloma cells exposed to bortezomib and lenalidomide. Eltrombopag stimulated megakaryopoiesis in human CD34+ cells from normal individuals and from patients with relapsed multiple myeloma via activation of Akt signaling pathways. These results provide proof-of-principle supporting the design of future clinical studies examining eltrombopag for the treatment of thrombocytopenia in patients with advanced multiple myeloma.