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• W4362547156 abstract "<div>Abstract<p><i>SF3B1</i> mutations, which occur in 20% of patients with myelodysplastic syndromes (MDS), are the hallmarks of a specific MDS subtype, MDS with ringed sideroblasts (MDS-RS), which is characterized by the accumulation of erythroid precursors in the bone marrow and primarily affects the elderly population. Here, using single-cell technologies and functional validation studies of primary <i>SF3B1</i>-mutant MDS-RS samples, we show that <i>SF3B1</i> mutations lead to the activation of the EIF2AK1 pathway in response to heme deficiency and that targeting this pathway rescues aberrant erythroid differentiation and enables the red blood cell maturation of MDS-RS erythroblasts. These data support the development of EIF2AK1 inhibitors to overcome transfusion dependency in patients with <i>SF3B1</i>-mutant MDS-RS with impaired red blood cell production.</p>Significance:<p>MDS-RS are characterized by significant anemia. Patients with MDS-RS die from a shortage of red blood cells and the side effects of iron overload due to their constant need for transfusions. Our study has implications for the development of therapies to achieve long-lasting hematologic responses.</p><p><i><a href=https://aacrjournals.org/bloodcancerdiscov/article/doi/10.1158/2643-3230.BCD-3-6-ITI target=_blank>This article is highlighted in the In This Issue feature, p. 476</a></i></p></div>" @default.
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• W4362547156 date "2023-04-04" @default.
• W4362547156 modified "2023-10-15" @default.
• W4362547156 title "Data from Targeting the EIF2AK1 Signaling Pathway Rescues Red Blood Cell Production in <i>SF3B1</i>-Mutant Myelodysplastic Syndromes With Ringed Sideroblasts" @default.
• W4362547156 doi "https://doi.org/10.1158/2643-3230.c.6550976.v1" @default.
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