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Title: Physiologic expression of Sf3b1K700E causes impaired erythropoieses, aberrant splicing, and sensitivity to pharmacologic spliceosome modulation      
keywords:
Transcriptome or Gene expression
ID:
PRJNA339149
description:
Over 80% of patients with the refractory anemia with ring sideroblasts subtype of myelodysplastic syndrome (MDS) have mutations in Splicing Factor 3B, Subunit 1 (SF3B1). We generated a conditional knock-in mouse model of the most common SF3B1 mutation, Sf3b1K700E. Sf3b1K700E mice develop macrocytic anemia due to a terminal erythroid maturation defect, erythroid dysplasia, and long-term hematopoietic stem cell (LT-HSC) expansion. Sf3b1K700E myeloid progenitors and SF3B1-mutant MDS patient samples demonstrate aberrant 3' splice-site selection associated with increased nonsense-mediated decay. Tet2 loss cooperates with Sf3b1K700E to cause a more severe erythroid and LT-HSC phenotype. Furthermore, the spliceosome modulator, E7017, selectively kills Sf3b1K700E-expressing cells. Thus, Sf3b1K700E expression reflects the phenotype of the mutation in MDS and may be a therapeutic target in MDS. Overall design: 15 samples, including 6 mouse and 9 human samples with varying SF3B1 status
accesstypes:
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landingpage: http://www.ncbi.nlm.nih.gov/bioproject/PRJNA339149
authentication:
none
authorization:
none
ID:
pmid:27622333
abbreviation:
NCBI
homePage: http://www.ncbi.nlm.nih.gov
ID:
SCR:006472
name:
National Center for Biotechnology Information
homePage: http://www.ncbi.nlm.nih.gov/bioproject
ID:
SCR:004801
name:
NCBI BioProject
  • R24 DK099808/DK/NIDDK NIH HHS/United States

  • R01 HL082945/HL/NHLBI NIH HHS/United States

  • R24 DK094746/DK/NIDDK NIH HHS/United States

  • R01 CA184922/CA/NCI NIH HHS/United States

  • R01 DK087992/DK/NIDDK NIH HHS/United States

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