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BCL-2 Family Of Genes Is a Key Regulator In The Pathogenesis Of SF3B1 Mutant and Wild Type MDS With Ring Sideroblasts and Represents a Novel Drug Target In This Disease
- Source :
- Blood. 122:263-263
- Publication Year :
- 2013
- Publisher :
- American Society of Hematology, 2013.
-
Abstract
- Myelodysplastic syndromes (MDS) are a group of neoplastic diseases characterized by impairment in hematopoietic cell differentiation which leads to disease related consequences like cytopenias and cellular dysplasia. Mutations in splicing factor 3b subunit 1 (SF3B1) are the most frequently identified genetic abnormalities in refractory anemia with ring sideroblasts (RARS) and RARS with thrombocytosis (RARS-T). However, the mechanisms whereby cells acquire clonal dominance and evolution, cytopenias and impairment in differentiation remain unknown. To understand the role of SF3B1 mutations in the pathogenesis of RARS/-T, we analyzed the transcriptome of SF3B1 mutant (MUT) and wild type (WT) RARS/-T patients (pts). RNA was isolated from bone marrow of healthy subjects (n=3), SF3B1 MUT (n=3) and WT (n=3) RARS/-T, and other MDS (n=5). cDNA was made from RNA (1.5-3ug) and fragmented for library preparation. RNA-sequencing was performed on 20 million sequence reads on an Illumina HiSeq2000 and aligned to the human genome 19. RNA-splicing patterns were analyzed by a published bioinformatics algorithm at three levels (exon usage, gene expression, and pathway analysis) (Visconte V; Blood. 2012). Differential exon usage identified 271 and 71 genes with at least 1 exon alternatively spliced in SF3B1 MUT, WT, and healthy subjects (P Disclosures: No relevant conflicts of interest to declare.
Details
- ISSN :
- 15280020 and 00064971
- Volume :
- 122
- Database :
- OpenAIRE
- Journal :
- Blood
- Accession number :
- edsair.doi...........90d317e763a34900fc7912a37b5c5119