Effect of the nonpeptide thrombopoietin receptor agonist eltrombopag on megakaryopoiesis of patients with lower risk myelodysplastic syndrome

• Published in: Leukemia research 2011-03, Vol.35 (3), p.323-328
• Main Authors: Mavroudi, Irene, Pyrovolaki, Katerina, Pavlaki, Konstantia, Kozana, Androniki, Psyllaki, Maria, Kalpadakis, Christina, Pontikoglou, Charalampos, Papadaki, Helen A
• Format: Article
• Language: English
• Subjects: Aged; Aged, 80 and over; Antigens, CD34 - metabolism; Apoptosis - drug effects; Benzoates - therapeutic use; Blotting, Western; Bone Marrow Cells - drug effects; Bone Marrow Cells - pathology; Cell Proliferation - drug effects; Eltrombopag; Female; Hematology, Oncology and Palliative Medicine; Humans; Hydrazines - therapeutic use; Male; Megakaryocyte Progenitor Cells - drug effects; Megakaryocyte Progenitor Cells - pathology; Megakaryopoiesis; Middle Aged; Myelodysplastic syndrome; Myelodysplastic Syndromes - drug therapy; Myelodysplastic Syndromes - pathology; Pyrazoles - therapeutic use; Receptors, Thrombopoietin - agonists; Risk Factors; Thrombocytopenia; Thrombopoiesis - drug effects; Thrombopoietin; Tumor Cells, Cultured
• ISSN: 0145-2126; 1873-5835
• DOI: 10.1016/j.leukres.2010.06.029

Abstract Eltrombopag is a nonpeptidyl thrombopoietin receptor agonist. We evaluated the ex vivo effect of eltrombopag on megakaryopoiesis of patients with lower risk myelodysplastic syndromes (MDSs). At a concentration of 0.1 μg/mL, eltrombopag resulted in a significant increase in the number of megakaryocytic colonies in MDS patients and healthy controls compared to baseline. This dose of eltrombopag did not exert any significant change in the proliferation rate or the survival characteristics of patient CD34+ cells that might clinically imply an unfavorable effect on patients’ outcome. These encouraging preclinical data support the rationale of using eltrombopag in the clinic for alleviation of thrombocytopenia in lower risk MDS patients.