ArticleJournal of hematology & oncology2014
Splicing factor 3b subunit 1 (Sf3b1) haploinsufficient mice display features of low risk Myelodysplastic syndromes with ring sideroblasts.
Article in Journal of hematology & oncology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 21 citations in OpenAlex.
- The genetics of myelodysplastic syndromes and the opportunities for tailored treatments.Frontiers in oncology · 2022Review
- Review
- Roles and mechanisms of alternative splicing in cancer - implications for care.Nature reviews. Clinical oncology · 2020Review
- [Features and clinical significance of gene mutations in patients with myelodysplastic syndromes with ring sideroblasts].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2020Article
- Abnormal Ferroptosis in Myelodysplastic Syndrome.Frontiers in oncology · 2020Article
- Smc3 is required for mouse embryonic and adult hematopoiesis.Experimental hematology · 2019Article
- SF3B1 deficiency impairs human erythropoiesis via activation of p53 pathway: implications for understanding of ineffective erythropoiesis in MDS.Journal of hematology & oncology · 2018Article
- Article
- Splicing factor mutations in MDS RARS and MDS/MPN-RS-T.International journal of hematology · 2017Review
- Complete mutational spectrum of the autophagy interactome: a novel class of tumor suppressor genes in myeloid neoplasms.Leukemia · 2017Article
- Physiologic Expression of Sf3b1(K700E) Causes Impaired Erythropoiesis, Aberrant Splicing, and Sensitivity to Therapeutic Spliceosome Modulation.Cancer cell · 2016Article
- Spliceosomal component Sf3b1 is essential for hematopoietic differentiation in zebrafish.Experimental hematology · 2016Article
- GEP analysis validates high risk MDS and acute myeloid leukemia post MDS mice models and highlights novel dysregulated pathways.Journal of hematology & oncology · 2016Article
- Revisiting the case for genetically engineered mouse models in human myelodysplastic syndrome research.Blood · 2015Review
- Mutation analysis of Chinese sporadic congenital sideroblastic anemia by targeted capture sequencing.Journal of hematology & oncology · 2015Article
- Pathogenesis of myelodysplastic syndromes: an overview of molecular and non-molecular aspects of the disease.Blood research · 2014Review
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Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
Abstract
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.
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