Faculty, Staff and Student Publications
Publication Date
11-2-2022
Journal
Blood Cancer Discvoery
Abstract
SF3B1 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 SF3B1-mutant MDS-RS samples, we show that SF3B1 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 SF3B1-mutant MDS-RS with impaired red blood cell production.
Keywords
Humans, Aged, RNA Splicing Factors, Phosphoproteins, Myelodysplastic Syndromes, Erythroid Precursor Cells, Signal Transduction, eIF-2 Kinase
Included in
Bioinformatics Commons, Biomedical Informatics Commons, Hematology Commons, Hemic and Lymphatic Diseases Commons, Internal Medicine Commons, Medical Sciences Commons
Comments
Supplementary Materials
PMID: 35926182