Transcriptomics

Dataset Information

328

RNA-seq of bone marrow CD34+ cells from myelodysplastic syndrome patients with and without SF3B1 mutation and from healthy controls


ABSTRACT: The splicing factor SF3B1 is the most commonly mutated gene in the myelodysplastic syndromes (MDS), particularly in patients with refractory anemia with ring sideroblasts (RARS). MDS is a disorder of the hematopoietic stem cell and we thus studied the transcriptome of CD34+ cells from MDS patients with SF3B1 mutations using RNA-sequencing. Genes significantly differentially expressed at the transcript and/or exon level in SF3B1 mutant compared to wildtype cases include genes involved in MDS pathogenesis (ASXL1, CBL), iron homeostasis and mitochondrial metabolism (ALAS2, ABCB7, SLC25A37) and RNA splicing/processing (PRPF8, HNRNPD). Many genes regulated by a DNA damage-induced BRCA1-BCLAF1-SF3B1 protein complex showed differential expression/splicing in SF3B1 mutant cases. Our data indicate that SF3B1 plays a critical role in MDS by affecting the expression and splicing of genes involved in specific cellular processes/pathways, many of which are relevant to the known RARS pathophysiology, suggesting a causal link. RNA-Seq was performed to compare the transcriptome of bone marrow CD34+ cells from eight MDS patients with SF3B1 mutation, four MDS patients with no known splicing mutation and five healthy controls.

ORGANISM(S): Homo sapiens  

SUBMITTER: Hamid Dolatshad   Andrea Pellagatti 

PROVIDER: E-GEOD-63569 | ArrayExpress | 2014-11-22

SECONDARY ACCESSION(S): SRP050146GSE63569PRJNA268220

REPOSITORIES: GEO, ArrayExpress, ENA

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Publications

Disruption of SF3B1 results in deregulated expression and splicing of key genes and pathways in myelodysplastic syndrome hematopoietic stem and progenitor cells.

Dolatshad H H   Pellagatti A A   Fernandez-Mercado M M   Yip B H BH   Malcovati L L   Attwood M M   Przychodzen B B   Sahgal N N   Kanapin A A AA   Lockstone H H   Scifo L L   Vandenberghe P P   Papaemmanuil E E   Smith C W J CW   Campbell P J PJ   Ogawa S S   Maciejewski J P JP   Cazzola M M   Savage K I KI   Boultwood J J  

Leukemia 20141127 5


The splicing factor SF3B1 is the most commonly mutated gene in the myelodysplastic syndrome (MDS), particularly in patients with refractory anemia with ring sideroblasts (RARS). We investigated the functional effects of SF3B1 disruption in myeloid cell lines: SF3B1 knockdown resulted in growth inhibition, cell cycle arrest and impaired erythroid differentiation and deregulation of many genes and pathways, including cell cycle regulation and RNA processing. MDS is a disorder of the hematopoietic  ...[more]

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