title: The non-peptide thrombopoietin receptor agonist eltrombopag stimulates megakaryopoiesis in bone marrow cells from patients with relapsed multiple myeloma.
abstract: 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.
authors.affiliation: Division of Hematology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. jyjeong@kosin.ac.kr.|Department of Biochemistry, Kosin University College of Medicine, Busan, South Korea. jyjeong@kosin.ac.kr.|Cancer Research Institute, Kosin University College of Medicine, Busan, South Korea. jyjeong@kosin.ac.kr.
authors.forename: Jee-Yeong
authors.initials: JY
authors.lastname: Jeong
authors.affiliation: Division of Hematology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. levine.michelle.s@gmail.com.
authors.forename: Michelle S
authors.initials: MS
authors.lastname: Levine
authors.affiliation: Division of Hematology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. nirabaya@hotmail.com.
authors.forename: Nirmalee
authors.initials: N
authors.lastname: Abayasekara
authors.affiliation: Division of Hematology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. nberliner@partners.org.
authors.forename: Nancy
authors.initials: N
authors.lastname: Berliner
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. jacobp_laubach@dfci.harvard.edu.
authors.forename: Jacob
authors.initials: J
authors.lastname: Laubach
authors.affiliation: Division of Hematology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. gvanasse@partners.org.|Present address: Translational Clinical Oncology, Novartis Institutes for Biomedical Research, Inc., Cambridge, MA, USA. gvanasse@partners.org.
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Vanasse
mesh_terms: D001565:Benzoates / Q000494:pharmacology*; D045744:Cell Line, Tumor; D006410:Hematopoiesis / Q000187:drug effects*; D006801:Humans; D006834:Hydrazines / Q000494:pharmacology*; D066298:In Vitro Techniques; D008533:Megakaryocytes / Q000187:drug effects*; D009101:Multiple Myeloma / Q000150:complications*; D009364:Neoplasm Recurrence, Local / Q000150:complications; D011720:Pyrazoles / Q000494:pharmacology*; D053628:Receptors, Thrombopoietin / Q000819:agonists; D013921:Thrombocytopenia / Q000188:drug therapy* / Q000209:etiology
chemical_list: D001565:Benzoates; D006834:Hydrazines; D011720:Pyrazoles; D053628:Receptors, Thrombopoietin; C520809:eltrombopag