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- Title
Biological basis for efficacy of activin receptor ligand traps in myelodysplastic syndromes.
- Authors
Verma, Amit; Suragani, Rajasekhar N. V. S.; Aluri, Srinivas; Shah, Nishi; Bhagat, Tushar D.; Alexander, Mark J.; Komrokji, Rami; Kumar, Ravi; Suragani, Rajasekhar Nvs
- Abstract
Signaling by the TGF-β superfamily is important in the regulation of hematopoiesis and is dysregulated in myelodysplastic syndromes (MDSs), contributing to ineffective hematopoiesis and clinical cytopenias. TGF-β, activins, and growth differentiation factors exert inhibitory effects on red cell formation by activating canonical SMAD2/3 pathway signaling. In this Review, we summarize evidence that overactivation of SMAD2/3 signaling pathways in MDSs causes anemia due to impaired erythroid maturation. We also describe the basis for biological activity of activin receptor ligand traps, novel fusion proteins such as luspatercept that are promising as erythroid maturation agents to alleviate anemia and related comorbidities in MDSs and other conditions characterized by impaired erythroid maturation.
- Subjects
ACTIVIN receptors; MYELODYSPLASTIC syndromes; CHIMERIC proteins; ERYTHROCYTES; GROWTH factors; REGULATION of hematopoiesis; CELLULAR signal transduction; ANEMIA prevention; ERYTHROPOIESIS
- Publication
Journal of Clinical Investigation, 2020, Vol 130, Issue 2, p582
- ISSN
0021-9738
- Publication type
journal article
- DOI
10.1172/JCI133678