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| Status |
Public on Aug 17, 2016 |
| Title |
Physiologic expression of Sf3b1K700E causes impaired erythropoieses, aberrant splicing, and sensitivity to pharmacologic spliceosome modulation |
| Organisms |
Homo sapiens; Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
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.
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| Overall design |
15 samples, including 6 mouse and 9 human samples with varying SF3B1 status
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| Contributor(s) |
Seiler M, Obeng E |
| Citation(s) |
27622333 |
| Submission date |
Aug 16, 2016 |
| Last update date |
May 15, 2019 |
| Contact name |
Silvia Buonamici |
| Organization name |
H3 Biomedicine
|
| Street address |
300 Technology Square #5
|
| City |
Cambridge |
| State/province |
MA |
| ZIP/Postal code |
02139 |
| Country |
USA |
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| Platforms (2) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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| Samples (15)
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| Relations |
| BioProject |
PRJNA339149 |
| SRA |
SRP082227 |
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