|
MYELODYSPLASTIC SYNDROME
|
0.800 |
GeneticVariation
|
group |
BEFREE |
Mutations of splice factors SF3B1, SRSF2, ZRSR2 and U2AF1 occur in >50% of MDS.
|
31680297 |
2020 |
|
MYELODYSPLASTIC SYNDROME
|
0.800 |
GeneticVariation
|
group |
BEFREE |
MacroH2A1.1 mRNA levels are significantly decreased in patients with low-risk MDS presenting with chromosomal 5q deletion and myeloid cytopenias and tend to be decreased in MDS patients carrying the U2AF1 S34F mutation.
|
31439048 |
2019 |
|
MYELODYSPLASTIC SYNDROME
|
0.800 |
GeneticVariation
|
group |
BEFREE |
U2 small nuclear RNA auxiliary factor 1 (U2AF1) mutant is the most common molecular biological abnormality in patients with myelodysplastic syndromes.
|
31754743 |
2019 |
|
MYELODYSPLASTIC SYNDROME
|
0.800 |
AlteredExpression
|
group |
BEFREE |
Collectively, mutations in U2AF1 induce expression of therapeutically targetable 'active' IRAK4 isoforms and provide a genetic link to activation of chronic innate immune signalling in MDS and AML.
|
31011167 |
2019 |
|
MYELODYSPLASTIC SYNDROME
|
0.800 |
GeneticVariation
|
group |
BEFREE |
Contrary to previous reports, we found no association between TET2 mutations and HMA treatment response (40% vs 41%; P = 0.9), even in the absence of ASXL1 mutations (P = 0.4).We conclude that ASXL1 mutations in MDS predict inferior response to treatment with both HMAs and LEN; response to LEN was also compromised by U2AF1 mutations and high risk karyotype; SF3B1 mutations identified patients likely to respond to LEN.
|
30152885 |
2018 |
|
MYELODYSPLASTIC SYNDROME
|
0.800 |
GeneticVariation
|
group |
BEFREE |
Taken together, our results demonstrate that ATR may represent a novel therapeutic target in patients with MDS carrying the U2AF1(S34F) mutation and potentially other malignancies harboring spliceosome mutations.<b>Significance:</b> This study provides preclinical evidence that patients with MDS or other myeloid malignancies driven by spliceosome mutations may benefit from ATR inhibition to exploit the R loop-associated vulnerability induced by perturbations in splicing.<i></i>.
|
30054334 |
2018 |
|
MYELODYSPLASTIC SYNDROME
|
0.800 |
GeneticVariation
|
group |
BEFREE |
The aim of this study was to investigate the clinical and biological implications of different U2AF1 mutation types in MDS.
|
29057546 |
2018 |
|
MYELODYSPLASTIC SYNDROME
|
0.800 |
GeneticVariation
|
group |
BEFREE |
Mutations affecting the spliceosomal protein U2AF1 are commonly found in myelodysplastic syndromes (MDS) and secondary acute myeloid leukemia (sAML).
|
30322915 |
2018 |
|
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 |
We infer that U2AF1 S34 mutations characterize a distinct subgroup of MDS: younger age of onset and differential associations with particular cytogenetic aberrations depending on specific mutations [S34Y to +8; S34F to +8 and del(20q)].
|
28938223 |
2017 |
|
MYELODYSPLASTIC SYNDROME
|
0.800 |
GeneticVariation
|
group |
BEFREE |
Mutations of the splicing factor-encoding gene U2AF1 are frequent in the myelodysplastic syndromes (MDS), a myeloid malignancy, and other cancers.
|
28436936 |
2017 |
|
MYELODYSPLASTIC SYNDROME
|
0.800 |
GeneticVariation
|
group |
CLINVAR |
Identifying recurrent mutations in cancer reveals widespread lineage diversity and mutational specificity.
|
26619011 |
2016 |
|
MYELODYSPLASTIC SYNDROME
|
0.800 |
AlteredExpression
|
group |
BEFREE |
With the advent of next generation sequencing, recurrent somatic mutations in genes involved in epigenetic regulation (TET2, ASXL1, EZH2, DNMT3A, IDH1/2), RNA splicing (SF3B1, SRSF2, U2AF1, ZRSR2), DNA damage response (TP53), transcriptional regulation (RUNX1, BCOR, ETV6) and signal transduction (CBL, NRAS, JAK2) have been identified in MDS.
|
26769228 |
2016 |
|
MYELODYSPLASTIC SYNDROME
|
0.800 |
GeneticVariation
|
group |
BEFREE |
In total, 122 patients with MDS (30%), acute myeloid leukemia (51%), myeloproliferative neoplasms (MPN) (11%), and MDS/MPN (8%) receiving a HCT from 2003 to 2012 were evaluated for mutations in U2AF1 and SRSF2 by direct sequencing.
|
26799334 |
2016 |
|
MYELODYSPLASTIC SYNDROME
|
0.800 |
GeneticVariation
|
group |
BEFREE |
MDS and acute myeloid leukemia patient samples harboring U2AF35(S34F) have a similar increased use of the ATG7 distal CP site, and previous studies have shown that mice with hematopoietic cells lacking Atg7 develop an MDS-like syndrome.
|
27184077 |
2016 |
|
MYELODYSPLASTIC SYNDROME
|
0.800 |
GeneticVariation
|
group |
BEFREE |
These data suggest that the S34F mutation alters U2AF1 function in the context of specific RNA sequences, leading to aberrant alternative splicing of target genes, some of which may be relevant for MDS pathogenesis.
|
25311244 |
2015 |
|
MYELODYSPLASTIC SYNDROME
|
0.800 |
GeneticVariation
|
group |
BEFREE |
The U2AF1 mutation was associated with inferior OS in low-risk MDS patients (P = 0.035).
|
26115659 |
2015 |
|
MYELODYSPLASTIC SYNDROME
|
0.800 |
GeneticVariation
|
group |
BEFREE |
These findings support the hypothesis that mutant U2AF1 alters downstream gene isoform expression, thereby contributing to abnormal hematopoiesis in patients with MDS.
|
25965570 |
2015 |
|
MYELODYSPLASTIC SYNDROME
|
0.800 |
GeneticVariation
|
group |
UNIPROT |
These data suggest that the S34F mutation alters U2AF1 function in the context of specific RNA sequences, leading to aberrant alternative splicing of target genes, some of which may be relevant for MDS pathogenesis.
|
25311244 |
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 |
CLINVAR |
Clinical implications of U2AF1 mutation in patients with myelodysplastic syndrome and its stability during disease progression.
|
23861105 |
2013 |
|
MYELODYSPLASTIC SYNDROME
|
0.800 |
GeneticVariation
|
group |
BEFREE |
U2AF1 mutation is more prevalent in younger MDS patients and associated with inferior outcomes although it is stable during the clinical course.
|
23861105 |
2013 |
|
MYELODYSPLASTIC SYNDROME
|
0.800 |
Biomarker
|
group |
BEFREE |
Over the past few years, large-scale genomic studies of patients with myelodysplastic syndrome (MDS) and acute myelogenous leukemia (AML) have unveiled recurrent somatic mutations in genes involved in epigenetic regulation (DNMT3A, IDH1/2, TET2, ASXL1, EZH2 and MLL) and the spliceosomal machinery (SF3B1, U2AF1, SRSF2, ZRSR2, SF3A1, PRPF40B, U2AF2, and SF1).
|
23645565 |
2013 |
|
MYELODYSPLASTIC SYNDROME
|
0.800 |
Biomarker
|
group |
BEFREE |
Recurrent somatic mutations in splicing machinery components, including SF3B1, U2AF1 and SRSF2 genes have recently been reported in myelodysplastic syndromes (MDS).
|
23280334 |
2013 |
|
MYELODYSPLASTIC SYNDROME
|
0.800 |
GeneticVariation
|
group |
BEFREE |
SF3B1 mutations are prevalent in low-risk MDS with ring sideroblasts, whereas U2AF1 and SRSF2 mutations are frequent in chronic myelomonocytic leukemia and advanced forms of MDS.
|
22323480 |
2012 |