Splicing factor 3b subunit 1 (Sf3b1) haploinsufficient mice display features of low risk Myelodysplastic syndromes with ring sideroblasts

BackgroundThe presence of somatic mutations in splicing factor 3b subunit 1 (SF3B1) in patients with Myelodysplastic syndromes with ring sideroblasts (MDS-RS) highlights the importance of the RNA-splicing machinery in MDS. We previously reported the presence of bone marrow (BM) RS in Sf3b1 heterozygous (Sf3b1+/−) mice which are rarely found in mouse models of MDS. Sf3b1+/− mice were originally engineered to study the interaction between polycomb genes and other proteins.MethodsWe used routine blood tests and histopathologic analysis of BM, spleen, and liver to evaluate the hematologic and morphologic characteristics of Sf3b1+/− mice in the context of MDS by comparing the long term follow-up (15 months) of Sf3b1+/− and Sf3b1+/+ mice. We then performed a comprehensive RNA-sequencing analysis to evaluate the transcriptome of BM cells from Sf3b1+/− and Sf3b1+/+ mice.ResultsSf3b1+/− exhibited macrocytic anemia (MCV: 49.5 ± 1.6 vs 47.2 ± 1.4; Hgb: 5.5 ± 1.7 vs 7.2 ± 1.0) and thrombocytosis (PLTs: 911.4 ± 212.1 vs 878.4 ± 240.9) compared to Sf3b1+/+ mice. BM analysis showed dyserythropoiesis and occasional RS in Sf3b1+/− mice. The splenic architecture showed increased megakaryocytes with hyperchromatic nuclei, and evidence of extramedullary hematopoiesis. RNA-sequencing showed higher expression of a gene set containing Jak2 in Sf3b1+/− compared to Sf3b1+/+.ConclusionsOur study indicates that Sf3b1+/− mice manifest features of low risk MDS-RS and may be relevant for preclinical therapeutic studies.

• Publication year

  2014

• Venue

  Journal of Hematology & Oncology

• Publication date

  2014-12-07

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1186/s13045-014-0089-xPMID 25481243PMCID 4266210
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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