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

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.

• Authors: Anna Mies, Olivier Hermine, Uwe Platzbecker
• Journal: Current hematologic malignancy reports (Curr Hematol Malig Rep) Vol. 11 Issue 6 Pg. 416-424 (12 2016) ISSN: 1558-822X [Electronic] United States
• PMID: 27595736 (Publication Type: Journal Article, Review)

Chemical References

• ACE-011
• Immunoglobulin Fc Fragments
• Phosphoproteins
• RNA Splicing Factors
• Recombinant Fusion Proteins
• SF3B1 protein, human
• Transforming Growth Factor beta
• Activins
• luspatercept
• Activin Receptors, Type II

Topics

• Activin Receptors, Type II (antagonists & inhibitors, metabolism)
• Activins (therapeutic use)
• Humans
• Immunoglobulin Fc Fragments (therapeutic use)
• Iron Overload (complications, genetics, pathology)
• Myelodysplastic Syndromes (drug therapy, genetics, pathology)
• Phosphoproteins (genetics)
• RNA Splicing Factors (genetics)
• Recombinant Fusion Proteins (therapeutic use)
• Transforming Growth Factor beta (antagonists & inhibitors, metabolism)