Biological basis for efficacy of activin receptor ligand traps in myelodysplastic syndromes

Amit Verma, Rajasekhar N.V.S. Suragani, Srinivas Aluri, Nishi Shah, Tushar D. Bhagat, Mark J. Alexander, Rami Komrokji, Ravi Kumar

Research output: Contribution to journalReview article

4 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)582-589
Number of pages8
JournalJournal of Clinical Investigation
Volume130
Issue number2
DOIs
StatePublished - Feb 3 2020

ASJC Scopus subject areas

  • Medicine(all)

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