Project description:Eltrombopag, a small molecule thrombopoietin receptor (TPO-R) agonist and potent intracellular iron chelator, has shown remarkable efficacy to stimulate sustained multilineage hematopoiesis in patients with bone marrow failure syndromes, suggesting an effect at the most immature hematopoietic stem and multipotent progenitor level. While the functional and molecular effects of Eltrombopag on megakaryopoiesis have been carefully studied in the recent past, insights into its mechanistic impact on the earliest stages of hematopoiesis have been limited. Additionally, previous studies also revealed molecular pathway of Eltrombopag apart from stimulation of TPO signaling, detail characterization remains to be addressed. In this study, we investigated the effects of Eltrombopag, in comparison with TPO, on highly-purified primary hematopoietic stem cells (HSCs) from healthy human donors. The binding of Eltrombopag to TPO-R is species-specific to human and primate cells. we also utilized HSCs isolated mouse as separation-of-function models to directly assess the molecular effect of Eltrombopag on HSCs independent of TPOR stimulation.
Project description:Eltrombopag, a small molecule thrombopoietin receptor (TPO-R) agonist and potent intracellular iron chelator, has shown remarkable efficacy to stimulate sustained multilineage hematopoiesis in patients with bone marrow failure syndromes, suggesting an effect at the most immature hematopoietic stem and multipotent progenitor level. While the functional and molecular effects of Eltrombopag on megakaryopoiesis have been carefully studied in the recent past, insights into its mechanistic impact on the earliest stages of hematopoiesis have been limited. Additionally, previous studies also revealed molecular pathway of Eltrombopag apart from stimulation of TPO signaling, detail characterization remains to be addressed. In this study, we investigated the effects of Eltrombopag, in comparison with TPO, on highly-purified primary hematopoietic stem cells (HSCs) from healthy human donors. The binding of Eltrombopag to TPO-R is species-specific to human and primate cells. we also utilized HSCs isolated mouse as separation-of-function models to directly assess the molecular effect of Eltrombopag on HSCs independent of TPOR stimulation.
Project description:Identification of differentially expressed genes upon treatment with Eltrombopag in HL60 cells. HL60 cells were untreated, or treated with 3ug/ml of Eltrombopag for 36 hrs in RPMI with 10% FBS HL60 cells were untreated, or treated with 3ug/ml of Eltrombopag for 36 hrs in RPMI with 10% FBS
Project description:Identification of differentially expressed genes upon treatment with Eltrombopag in HL60 cells. HL60 cells were untreated, or treated with 3ug/ml of Eltrombopag for 36 hrs in RPMI with 10% FBS