Abstract 13784: Thrombopoietin Restores Megakaryopoiesis By Protecting Bone Marrow Endothelial Progenitor Cells Of Patients With Hematologic Malignancies Undergoing Chemotherapy

Introduction and Objective: Thrombocytopenia is the most common side effect of patients with hematologic malignancies undergoing chemotherapy. Platelet production depends on a good bone marrow (BM) microenvironment, especially the endothelial progenitor cells (EPC), which play an important role in angiogenesis and thus supporting megakaryopoiesis. However, little is known regarding the function of EPC in patients with hematologic malignancies. Therefore, the present study aimed to examine the role of EPC in angiogenesis and megakaryopoiesis, and the effect of thrombopoietin (TPO) on EPC in patients with hematologic malignancies. Methods: Twenty-three patients with ALL or AML, and ten age-matched healthy donors were recruited in the present study. EPCs were isolated from BM mononuclear cells. The cell count, proliferation, migration, and tube formation assays were conducted. Megakaryocytes were quantified by flow cytometry after coculturing with EPC in the absence and presence of TPO (100 ng/ml). In addition, transgenic zebrafish with vascular endothelial cells expressing EGFP [Tg(fli-1:EGFP)] were used to examine the angiogenic effect of TPO. Simvastatin was used to induce vascular defects in zebrafish embryos. The embryos were then treated with or without TPO (10 -3 U/μl) by intravenous injection before fluorescent images were captured. Results: The number of BM EPC was significantly smaller in patients with ALL and AML than in healthy donors. The BM EPCs from patients showed significantly reduced proliferation, migration and tube formation when compared to those from healthy donors. TPO (100 ng/ml) significantly improved those functions of EPC, and significantly increased the number of megakaryocytes after coculture. In Tg(fli-1:EGFP) zebrafish embryos, TPO (10 -3 U/μl) significantly increased the SIV vascularized area in the presence of simvastatin. Conclusion: The present study shows that dysfunctional BM EPC contributes to the pathogenesis of thrombocytopenia in patients with hematologic malignancies undergoing chemotherapy; and such impaired functions of BM EPC could be restored by TPO. In addition, TPO increases the number of megakaryocytes after coculture with EPC in vitro and promotes angiogenesis in zebrafish embryos.