The non-peptide thrombopoietin receptor agonist eltrombopag stimulates megakaryopoiesis in bone marrow cells from patients with relapsed multiple myeloma

Journal of Hematology & Oncology

Gary J Vanasse²  Jacob Laubach⁴  Nancy Berliner¹  Nirmalee Abayasekara¹  Michelle S Levine¹  Jee-Yeong Jeong³ 

[1] Division of Hematology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA;Present address: Translational Clinical Oncology, Novartis Institutes for Biomedical Research, Inc., Cambridge, MA, USA;Cancer Research Institute, Kosin University College of Medicine, Busan, South Korea;Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA

关键词: CD138;    CD34;    Multiple myeloma;    Megakaryocytes;    Eltrombopag;   

Others  :  1174992
DOI  :  10.1186/s13045-015-0136-2

 received in 2014-12-29, accepted in 2015-04-04,  发布年份 2015

【 摘 要 】

Background

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.

Methods

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.

Results

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.

Conclusions

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.

【 授权许可】

   
2015 Jeong et al.; licensee Biomed Central.

【 图 表 】

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