Targeting the EIF2AK1 Signaling Pathway Rescues Red Blood Cell Production in SF3B1 Mutant Myelodysplastic Syndromes With Ringed Sideroblasts Vera Adema , Feiyang Ma, Rashmi Kanagal-Shamanna, Natthakan Thongon, Guillermo Montalban-Bravo, Hui Yang, Scott A. Peslak, Feng Wang, Pamela Acha, Francesc Sole, Pamela Lockyer, Margherita Cassari, Jaroslaw P. Maciejewski, Valeria Visconte, Irene Gañán-Gómez, Yuanbin Song, Carlos Bueso-Ramos, Matteo Pellegrini, Tuyet M. Tan, Rafael Bejar, Jennifer S. Carew, Stephanie Halene, Valeria Santini, GheathAl-Atrash, Karen Clise-Dwyer Guillermo Garcia-Manero, Gerd A. Blobel, and Simona Colla
Leading Edge of Cancer Research Symposium November 17-18, 2022
SF3B1 MT MDS-RS at the Single Cell Level
Ineffective erythropoiesis
Ringed Sideroblasts
SF3B1 MT
We profiled the hematopoietic landscape of SF3B1 MT MDS-RS at the single-cell level
Lin - CD34 + HSPCs
BM-MNCs
Ery
SF3B 1 MT Lin - CD34 + HSPCs:
Ery
Increased Ery/Mk differentiation Metabolic activation in SF3B1 -mutant cells
Increased Erythroblast at the Orthochromatic stage SF3B 1 MT MNCs:
EIF2AK1 Depletion Overcomes SF3B1 MT - Induced Arrest in Terminal Erythroid Differentiation
Depletion of EIF2AK1 induces differentiation of ringed sideroblasts. EIF2AK1 as a new pharmacological target for patients with MDS-RS with SF3B1 mutations
Terminally differentiated cells
Summary
V Adema et al., Blood Cancer Discov 2022
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