Physiologic expression of Sf3b1K700E causes impaired erythropoieses, aberrant splicing, and sensitivity to pharmacologic spliceosome modulation

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UID: 10889

Author(s): Seiler, Michael, Obeng, Esther A.

Description: Summary from GEO:

"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 from GEO:

"15 samples, including 6 mouse and 9 human samples with varying SF3B1 status."

Subject of Study

Subject(s)

OncoTree Cancer Type(s)

Myelodysplastic Syndromes

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