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. 2021 May 17;35(10):2936–2947. doi: 10.1038/s41375-021-01275-5

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© The Author(s) 2021

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Fig. 8 — High GDF-11 levels in the MDS BMME activate Smad2/3 phosphorylation and expression of Co-Smad4 that binds to the SDF-1 promoter region [7] thereby suppressing transcription and leading to impaired hematopoiesis. Trapping GDF-11 by RAP-536/luspatercept reduces Smad2/3 and Smad4 activity resulting in SDF-1 promoter activation and elevated expression, thereby restoring HSPC support.