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Activin Receptor II Ligand Traps and Their Therapeutic Potential in Myelodysplastic Syndromes with Ring Sideroblasts

  • Myelodysplastic Syndromes (D Steensma, Section Editor)
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Abstract

Distinct subtypes of lower risk myelodysplastic syndromes display ring sideroblasts in the bone marrow, i. e., erythroid progenitors characterized by excessive iron deposited in the mitochondria. This morphological feature is frequently associated with somatic mutations in components of the splicing machinery that constitutes the underlying molecular principle of the disease. Conventional treatment regimen with erythropoiesis-stimulating agents often fails to induce sustained erythroid improvement in these patients that harbor defects in late-stage erythroblasts downstream of erythropoietin action. In the present review, we will discuss activin receptor ligand traps as novel therapeutic strategies particularly for sideroblastic subgroups of myelodysplastic syndromes that were recently shown to alleviate anemia by specifically inhibiting aberrant TGF-β signaling and thereby promoting erythroid differentiation.

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Acknowledgments

This work was supported by the José Carreras Foundation (DJCLS R13/15) and a grant from the German Research Foundation (SFB655) (UP).

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Authors and Affiliations

  1. Department of Internal Medicine I, University Hospital Carl Gustav Carus, Technische Universität Dresden, Fetscherstraße 74, 01307, Dresden, Germany

    Anna Mies & Uwe Platzbecker

  2. Department of Hematology, Hôpital Necker, Assistance Publique Hôpitaux de Paris, University Paris Descartes and Imagine Institute, University Sorbonne Paris Cité, 24, boulevard du Montparnasse, 75015, Paris, France

    Olivier Hermine

  3. German Cancer Consortium (DKTK), Dresden and German Cancer Research Center (DKFZ), Heidelberg, Germany

    Uwe Platzbecker

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Anna Mies declares no potential conflicts of interest.

Olivier Hermine reports a research grant from Celgene.

Uwe Platzbecker reports research grants from Celgene and Acceleron.

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This article is part of the Topical Collection on Myelodysplastic Syndromes

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Mies, A., Hermine, O. & Platzbecker, U. Activin Receptor II Ligand Traps and Their Therapeutic Potential in Myelodysplastic Syndromes with Ring Sideroblasts. Curr Hematol Malig Rep 11, 416–424 (2016). https://doi.org/10.1007/s11899-016-0347-9

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