|
MYELODYSPLASTIC SYNDROME
|
0.800 |
GeneticVariation
|
group |
BEFREE |
More patients with mutated SF3B1 were lower-risk MDS.
|
29937400 |
2018 |
|
MYELODYSPLASTIC SYNDROME
|
0.800 |
GeneticVariation
|
group |
BEFREE |
We have used SF3b1 mutations associated with MDS to interrogate the role of the yeast ortholog, Hsh155, in BS selection and splicing.
|
28062854 |
2017 |
|
MYELODYSPLASTIC SYNDROME
|
0.800 |
GeneticVariation
|
group |
BEFREE |
Here we demonstrate that SF3B1 mutation(s) in our cohort of MDS patients with ring sideroblasts can arise from CD34(+)CD38(-)CD45RA(-)CD90(+)CD49f(+) HSCs and is an initiating event in disease pathogenesis.
|
26643973 |
2015 |
|
MYELODYSPLASTIC SYNDROME
|
0.800 |
GeneticVariation
|
group |
BEFREE |
The most common mutations found in MDS occur in genes involved in RNA splicing (including SF3B1, SRSF2, U2AF1, and ZRSR2) and epigenetic modification (including TET2, ASXL1, and DNMT3A).
|
25645650 |
2015 |
|
MYELODYSPLASTIC SYNDROME
|
0.800 |
GeneticVariation
|
group |
BEFREE |
Recent studies are shedding light on the molecular basis of myelodysplasia and how mutations and epimutations can induce and promote this neoplastic process through aberrant transcription factor function (RUNX1, ETV6, TP53), kinase signalling (FLT3, NRAS, KIT, CBL) and epigenetic deregulation (TET2, IDH1/2, DNMT3A, EZH2, ASXL1, SF3B1, U2AF1, SRSF2, ZRSR2).
|
24903747 |
2014 |
|
MYELODYSPLASTIC SYNDROME
|
0.800 |
GeneticVariation
|
group |
BEFREE |
To assess the impact of spliceosome mutations on splicing and to identify common pathways/genes affected by distinct mutations, we performed RNA-sequencing of MDS bone marrow samples harboring spliceosome mutations (including hotspot alterations of SF3B1, SRSF2 and U2AF1; small deletions of SRSF2 and truncating mutations of ZRSR2), and devoid of other common co-occurring mutations.
|
31680297 |
2020 |
|
MYELODYSPLASTIC SYNDROME
|
0.800 |
GeneticVariation
|
group |
BEFREE |
SF3B1 mutations are most frequent (~80%) in myelodysplastic syndromes (MDS) with ring sideroblasts (RS) but lack prognostic relevance.
|
23335386 |
2013 |
|
MYELODYSPLASTIC SYNDROME
|
0.800 |
GeneticVariation
|
group |
BEFREE |
Furthermore, SF3B1 mutations are independent predictors of favorable clinical outcome, and their incorporation into stratification systems might improve risk assessment in MDS.
|
21998214 |
2011 |
|
MYELODYSPLASTIC SYNDROME
|
0.800 |
GeneticVariation
|
group |
BEFREE |
Patient was initially diagnosed with low-risk myelodysplastic syndrome-refractory cytopenias and multilineage dysplasia (MDS-RCMD), progressed to AML after failing hypomethylating agent therapy.
|
28187034 |
2019 |
|
MYELODYSPLASTIC SYNDROME
|
0.800 |
GeneticVariation
|
group |
BEFREE |
In contrast, dysplastic features correlated with mutations usually encountered in MDS (for example, SF3B1 and U2AF1).
|
28555081 |
2017 |
|
MYELODYSPLASTIC SYNDROME
|
0.800 |
GeneticVariation
|
group |
BEFREE |
Another significant advance in MDS pathogenesis research is the recent identification of mutations in genes encoding transcription factors implicated in hematopoiesis and proteins involved in splicing (SF3B1), methylation (DNMT3A), regulation of methylation (TET2 and IDH), DNA conformation (EZH2 and ASXL1) and differentiation (N- and K-RAS).
|
23394086 |
2013 |
|
MYELODYSPLASTIC SYNDROME
|
0.800 |
GeneticVariation
|
group |
BEFREE |
Genotype-phenotype correlations have been observed, including the clustering of ring sideroblasts with SF3B1 mutations in MDS.
|
23327988 |
2012 |
|
MYELODYSPLASTIC SYNDROME
|
0.800 |
GeneticVariation
|
group |
BEFREE |
Inappropriately low hepcidin levels in patients with myelodysplastic syndrome carrying a somatic mutation of SF3B1.
|
23300182 |
2013 |
|
MYELODYSPLASTIC SYNDROME
|
0.800 |
GeneticVariation
|
group |
BEFREE |
RNA-sequencing analysis of SF3B1 mutants showed differentially used genes relevant in MDS pathogenesis, such as ASXL1, CBL, EZH, and RUNX families.
|
22826563 |
2012 |
|
MYELODYSPLASTIC SYNDROME
|
0.800 |
GeneticVariation
|
group |
BEFREE |
SF3B1, which encodes an essential spliceosomal protein, is frequently mutated in myelodysplastic syndromes (MDS) and many cancers.
|
31474574 |
2019 |
|
MYELODYSPLASTIC SYNDROME
|
0.800 |
GeneticVariation
|
group |
BEFREE |
Ring sideroblasts (RS) emerge as result of aberrant erythroid differentiation leading to excessive mitochondrial iron accumulation, a characteristic feature for myelodysplastic syndromes (MDS) with mutations in the spliceosome gene SF3B1.
|
31648334 |
2019 |
|
MYELODYSPLASTIC SYNDROME
|
0.800 |
GeneticVariation
|
group |
BEFREE |
Given that mRNA splicing and nuclear export are coordinated processes, we hypothesised that SF3B1 mutation might also affect export of certain mRNAs and that this may represent a targetable pathway for the treatment of SF3B1-mutant MDS.
|
30804405 |
2019 |
|
MYELODYSPLASTIC SYNDROME
|
0.800 |
GeneticVariation
|
group |
BEFREE |
In 2011, whole-exome sequencing studies showed recurrent somatic mutations of SF3B1 and other genes of the RNA splicing machinery in patients with myelodysplastic syndrome or myelodysplastic/myeloproliferative neoplasm.
|
23160465 |
2013 |
|
MYELODYSPLASTIC SYNDROME
|
0.800 |
GeneticVariation
|
group |
BEFREE |
Further, SF3B1 mutations were more frequently recurrent in the 33% of patients with MDS characterized with RS, whereas in other subtypes of MDS, only 2.3% of patients were detected with SF3B1 mutations (p=0.006).
|
23390883 |
2013 |
|
MYELODYSPLASTIC SYNDROME
|
0.800 |
GeneticVariation
|
group |
BEFREE |
To study their role in such disorders, we generated knock-in mice with hematopoietic-specific expression of Sf3b1-K700E, the commonest type of SF3B1 mutation in MDS.
|
27604819 |
2017 |
|
MYELODYSPLASTIC SYNDROME
|
0.800 |
GeneticVariation
|
group |
BEFREE |
Patients with U2AF1, SRSF2, and EZH2 mutations more commonly had high-risk than low-risk subtypes, while SF3B1 mutations were frequently confirmed in MDS subtypes with increased ring sideroblasts.
|
26508027 |
2016 |
|
MYELODYSPLASTIC SYNDROME
|
0.800 |
GeneticVariation
|
group |
BEFREE |
Patient samples showed SF3B1 K700E mutations within the ptDNA of 4 patients with acute leukemia and 3 with myelodysplastic syndrome who were known to harbor this mutation.
|
28615231 |
2017 |
|
MYELODYSPLASTIC SYNDROME
|
0.800 |
GeneticVariation
|
group |
BEFREE |
By contrast, mutations affecting spliceosome genes SF3B1 and SRSF2, closely associated with the myelodysplastic syndromes, were identified only in those aged >70 years, with several individuals harboring more than one such mutation.
|
25732814 |
2015 |
|
MYELODYSPLASTIC SYNDROME
|
0.800 |
GeneticVariation
|
group |
BEFREE |
Cases of MDS with ring sideroblasts unrelated to SF3B1 mutation were detected in the high-risk group.
|
30590617 |
2019 |
|
MYELODYSPLASTIC SYNDROME
|
0.800 |
GeneticVariation
|
group |
BEFREE |
Two myeloid neoplasms defined by the presence of RS, include refractory anemia with ring sideroblasts (RARS), now classified under myelodysplastic syndromes with RS (MDS-RS) and RARS with thrombocytosis (RARS-T); now called myelodysplastic/myeloproliferative neoplasm with RS and thrombocytosis (MDS/MPN-RS-T).
|
28188970 |
2017 |