Activin Receptor II Ligand Traps and Their Therapeutic Potential in Myelodysplastic Syndromes with Ring Sideroblasts.
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.
Department of Internal Medicine I, University Hospital Carl Gustav Carus, Technische Universität Dresden, Fetscherstraße 74, 01307, Dresden, Germany.
Anna
A
Mies
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
O
Hermine
Department of Internal Medicine I, University Hospital Carl Gustav Carus, Technische Universität Dresden, Fetscherstraße 74, 01307, Dresden, Germany. uwe.platzbecker@uniklinikum-dresden.de.|German Cancer Consortium (DKTK), Dresden and German Cancer Research Center (DKFZ), Heidelberg, Germany. uwe.platzbecker@uniklinikum-dresden.de.
Uwe
U
Platzbecker
D030301:Activin Receptors, Type II / Q000037:antagonists & inhibitors / Q000378:metabolism*; D028341:Activins / Q000627:therapeutic use; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000627:therapeutic use; D019190:Iron Overload / Q000150:complications / Q000235:genetics / Q000473:pathology; D009190:Myelodysplastic Syndromes / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D010750:Phosphoproteins / Q000235:genetics; D000072260:RNA Splicing Factors / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000378:metabolism
D030301:Activin Receptors, Type II; D028341:Activins; D007141:Immunoglobulin Fc Fragments; D010750:Phosphoproteins; D000072260:RNA Splicing Factors; D011993:Recombinant Fusion Proteins; D016212:Transforming Growth Factor beta; C542017:sotatercept; C112491:SF3B1 protein, human; C000621232:luspatercept
Activin receptor ligand trap; Luspatercept; MDS; Ring sideroblasts; SF3B1; TGF-β