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A potential role of erythropoietin in angiogenesis associated with myelodysplastic syndromes

Leukemia volume 16, page 1890 (2002)Cite this article

Bunworasate et al1 have recently published a brief report in which they described a transformation of a myelodysplastic syndrome (MDS) in an acute monoblastic leukemia in a patient 6 weeks after the initiation of erythropoietin (EPO) therapy for refractory anemia with ringed sideroblasts. Multiparameter flow cytometric analysis of bone marrow cells demonstrated coexpression of the EPO receptor with CD45 and CD13 on the surface of blasts.The incubation of marrow cells with EPO, compared to without, resulted in 1.3- and 1.6-fold increases, respectively, in tritiated thymidine incorporation and bromodeoxyuridine incorporation into CD13+ cells. The authors concluded that leukemic transformation in patients with EPO may be EPO-dependent and that management should consist of the discontinuation of EPO followed by observation, if clinically feasible.

In 1999 we published a paper in which we demonstrated a pro-angiogenic activity of EPO both in vitro and in vivo.2 We showed that an endothelial cell line expressed EPO receptors (EPORs) by Western blot analysis. Also EPO stimulated Janus kinase-2 (JAK-2) phosphorylation, cell proliferation, and matrix metalloproteinase-2 production in the endothelial cells and significantly enhanced their differentiation into vascular structures when seeded on Matrigel. In vivo, EPO induced a potent angiogenic response in the chick embryo chorioallantoic membrane (CAM) assay. Accordingly, endothelial cells of the CAM vasculature expressed EPORs and the angiogenic response of CAM blood vessels to EPO was comparable to that elicited by the prototypic angiogenic cyokine fibroblast growth factor-2 (FGF-2). Taken together, these data demonstrated the ability of EPO to interact directly with endothelial cells and to elicit an angiogenic response in vitro and in vivo and thus act as a bona fide direct angiogenic factor.

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  1. Department of Human Anatomy and Histology, University of Bari Medical School, Policlinico, Bari, Italy

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Ribatti, D. A potential role of erythropoietin in angiogenesis associated with myelodysplastic syndromes. Leukemia 16, 1890 (2002). https://doi.org/10.1038/sj.leu.2402623

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