Thrombocytopenia is a frequent symptom and clinical challenge in patients with myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Eltrombopag is a small molecule thrombopoietin receptor agonist that might be a new option to treat thrombocytopenia in these diseases, provided that it does not stimulate malignant hematopoiesis. In this work, AECC investigators Parekh, Verma, and Steidl studied the effects of Eltrombopag on proliferation, apoptosis, differentiation, colony formation, and malignant self-renewal of bone marrow mononuclear cells of patients with AML and MDS. They found that malignant bone marrow mononuclear cells did not show increased proliferation, or increased clonogenic capacity at concentrations of Eltrombopag ranging from 0.1 to 30 ug/ml. Rather, there was a moderate, but not significant (P = .18), decrease in the numbers of malignant cells (mean, 56%; SD, 28%). Eltrombopag did not increase 5-bromo-2-deoxyuridine incorporation, nor did it decrease apoptosis, nor increase of malignant self-renewal, or enhance in vivo engraftment in xenotransplantations. Eltrombopag was found to be capable of increasing megakaryocytic differentiation and formation of normal megakaryocytic colonies in patients with AML and MDS. These results provide a preclinical rationale for further testing of Eltrombopag for the treatment of thrombocytopenia in AML and MDS.