Prognostic value of U2AF1 mutant in patients with de novo myelodysplastic syndromes: a meta-analysis

Wang, Hong; Zhang, Nanchen; Wu, Xia; Zheng, Xue; Ling, Yantao; Gong, Yuping

doi:10.1007/s00277-019-03843-3

Cited by 22 publications

(20 citation statements)

References 33 publications

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“…Studies in lower-risk MDS have found U2AF1 not to be of significance after adjusting for risk adapted prognostic scores [169], while more recent data suggests U2AF1 (as well as several other genes) only to have independent prognostic value in patients with <5% blasts [170]. Finally, in a large meta-analysis of 3322 de novo MDS patients of which 390 patients had mutated U2AF1, the mutation did indeed have a prognostic impact on both OS and AML transformation [171].…”

Section: Ngs Mutational Screeningmentioning

confidence: 97%

Secondary Acute Myeloid Leukemia and the Role of Allogeneic Stem Cell Transplantation in a Population-Based Setting

Nilsson

Hulegårdh

Garelius

et al. 2019

Biology of Blood and Marrow Transplantation

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Secondary acute myeloid leukemia (s-AML) refers to patients with either therapy-related AML (t-AML), that is, AML after treatment with chemo-and/or radiation for a prior disease, or AML progressing from an antecedent hematologic disorder (AHD-AML), typically a myelodysplastic syndrome (MDS) or a myeloproliferative neoplasm. Patients with s-AML present with higher rates of adverse cytogenetic aberrations and higher frequencies of adverse mutations and, subsequently, respond worse to therapy, and have poorer outcome compared to de novo AML. To identify clinical and molecular factors that may improve prognostication is therefore of importance to guide clinical decision-making. The general aim of this thesis was to broaden the real-world knowledge of s-AML, regarding disease properties and outcome, using population-based registries, and additionally to investigate the importance of mutations in the transformation from MDS to AML. The research papers presented herein cover mutational screening in MDS and s-AML (study I), general characteristics and outcome of s-AML (study II), the role of allogeneic hematopoietic cell transplantation (HCT) in patients with s-AML (study III), and the epidemiology and treatment outcome specifically for t-AML (study IV). långtidsöverlevare utan transplantation. Att genomgå transplantation i s.k. första remission var överlägset behandling med enbart cytostatika. Studie IV fokuserade på patienter med terapirelaterad AML. Data från svenska AMLregistret på 686 patienter kombinerades med data från Socialstyrelsens cancerregister och Svensk Reumatologis Kvalitetsregister. Huvudsakliga fynd var att incidensen av t-AML tydligt ökar över tid och att andelen terapirelaterad AML av AML-fallen totalt blev allt större. Överlevnaden vid terapirelaterad AML var generellt mycket dyster, men i vissa genetiska undergrupper var den bättre och jämförbar med patienter med motsvarande genetisk riskprofil som nyinsjuknat i AML. Sammanfattningsvis är sekundär-AML en ovanlig sjukdom som är mycket svårbehandlad. Nya läkemedel kommer att krävas för att förbättra överlevnaden, men förhoppningsvis kommer sådana att utvecklas hand i hand med den ökade förståelsen av sjukdomsbiologin. Behandlingen av AML har i stort sett varit oförändrad i årtionden, men nyligen har läkemedel som bl.a. utnyttjar specifika genetiska avvikelser introducerats. Inom andra cancerformer har immun-och cellterapi fått stort genomslag och dessa är potentiellt användbara även mot AML. För gruppen med sekundär-AML är det därför av stor betydelse att sjukdomshistorik, hög ålder och samsjuklighet inte utgör hinder för deltagande i kommande läkemedelsstudier. LIST OF SCIENTIFIC PAPERS I. High-throughput mutational screening adds clinically important information in myelodysplastic syndromes and secondary or therapy-related acute myeloid leukemia.

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Section: Ngs Mutational Screeningmentioning

confidence: 97%

Secondary Acute Myeloid Leukemia and the Role of Allogeneic Stem Cell Transplantation in a Population-Based Setting

Nilsson

Hulegårdh

Garelius

et al. 2019

Biology of Blood and Marrow Transplantation

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“…Remarkably, a large number of U2AF1 mutational landscapes in various hematologic tumors have been reported, including MDS, MDS/MPN, MPN, AML, and chronic myeloid leukemia (CML). Here, we summarize U2AF1 mutations in patients with hematologic malignancies detected by Sanger sequencing, next-generation sequencing, and other mutation scanning technologies from 27 studies [ 11 , 12 , 13 , 21 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 ]. Among them, one meta-analysis that includes 13 studies with 3038 patients and another meta-analysis that includes 14 studies with 3322 patients reported an overall incidence of the U2AF1 mutant of 11.7% in MDS patients [ 32 , 33 ].…”

Section: U2af1 Mutations In Myeloid Malignanciesmentioning

confidence: 99%

“…Here, we summarize U2AF1 mutations in patients with hematologic malignancies detected by Sanger sequencing, next-generation sequencing, and other mutation scanning technologies from 27 studies [ 11 , 12 , 13 , 21 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 ]. Among them, one meta-analysis that includes 13 studies with 3038 patients and another meta-analysis that includes 14 studies with 3322 patients reported an overall incidence of the U2AF1 mutant of 11.7% in MDS patients [ 32 , 33 ]. U2AF1 mutation frequencies in these studies were 5–21.7% in MDS, 3.4–12.3% in AML, 0–8% in CML, 1.2–8% in MPN, and 5.7–14.5% in MDS/MPN overlap patients.…”

Section: U2af1 Mutations In Myeloid Malignanciesmentioning

confidence: 99%

The Biological and Clinical Consequences of RNA Splicing Factor U2AF1 Mutation in Myeloid Malignancies

Zhao

Cai²,

et al. 2022

Cancers

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Mutations of spliceosome genes have been frequently identified in myeloid malignancies with the large-scale application of advanced sequencing technology. U2 small nuclear RNA auxiliary factor 1 (U2AF1), an essential component of U2AF heterodimer, plays a pivotal role in the pre-mRNA splicing processes to generate functional mRNAs. Over the past few decades, the mutation landscape of U2AF1 (most frequently involved S34 and Q157 hotspots) has been drawn in multiple cancers, particularly in myeloid malignancies. As a recognized early driver of myelodysplastic syndromes (MDSs), U2AF1 mutates most frequently in MDS, followed by acute myeloid leukemia (AML) and myeloproliferative neoplasms (MPNs). Here, for the first time, we summarize the research progress of U2AF1 mutations in myeloid malignancies, including the correlations between U2AF1 mutations with clinical and genetic characteristics, prognosis, and the leukemic transformation of patients. We also summarize the adverse effects of U2AF1 mutations on hematopoietic function, and the alterations in downstream alternative gene splicing and biological pathways, thus providing comprehensive insights into the roles of U2AF1 mutations in the myeloid malignancy pathogenesis. U2AF1 mutations are expected to be potential novel molecular markers for myeloid malignancies, especially for risk stratification, prognosis assessment, and a therapeutic target of MDS patients.

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“…Currently, the effect of U2AF1 on the MDS prognosis is not clear. Some studies show that U2AF1 mutation has no effect on prognosis 9 – 11 , other studies show that U2AF1 gene mutation with poor prognosis 12 – 15 . Studies show that U2AF1 mutation sites may affect the prognosis.…”

Section: Introductionmentioning

confidence: 99%

Differential U2AF1 mutation sites, burden and co-mutation genes can predict prognosis in patients with myelodysplastic syndrome

Wang

Guo

Dong

et al. 2020

Sci Rep

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To investigate the U2AF1 gene mutation site, mutation load and co-mutations genes in patients with myelodysplastic syndrome (MDS) and their effects on prognosis. Gene mutation detection by next-generation sequence and related clinical data of 234 MDS patients were retrospectively collected and analyzed for the relationship between the clinical characteristics, treatment efficacy and prognosis of U2AF1 gene mutation. Among the 234 MDS patients, the U2AF1 gene mutation rate was 21.7% (51 cases), and the median variant allele frequency was 39.5%. Compared with the wild type, the U2AF1 mutant had a higher incidence of chromosome 8 aberration, and was positively correlated with the occurrence of ASXL1, RUNX1, SETBP1 gene mutation, negatively correlated with SF3B1, NPM1 genes mutation (p < 0.05). The most common mutation site of U2AF1 was S34F (32 cases), while U2AF1 Q157P site mutations had a higher incidence of chromosome 7 abnormalities (p = 0.003). The U2AF1 gene mutation more frequently coincided with signal pathway related gene mutations (p = 0.043) with a trend of shortened overall survival. Among patients with U2AF1 gene mutations, those with ASXL1 mutations were prone to develop into acute myeloid leukemia, those with RUNX1 mutations had an increased risk of relapse, and those with TET2 mutations had higher 1-year survival rate. Compared with the patient group of lower mutation load (VAF ≤ 40%), the group with higher mutation load of U2AF1 (VAF > 40%) had a significantly lower 1-year survival rate (46.1% and 80.5%, p = 0.027). The criteria of U2AF1 VAF > 40% is an independent indicator for poor prognosis of MDS patients. VAF > 40% of U2AF1 is an independent factor of short OS in MDS patients. MDS patients with a mutation in the Q157P site of U2AF1 and a higher U2AF1 mutation load suggests poor prognosis, and co-mutated genes in U2AF1 can affect disease progression and prognosis.

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Prognostic value of U2AF1 mutant in patients with de novo myelodysplastic syndromes: a meta-analysis

Cited by 22 publications

References 33 publications

Secondary Acute Myeloid Leukemia and the Role of Allogeneic Stem Cell Transplantation in a Population-Based Setting

Secondary Acute Myeloid Leukemia and the Role of Allogeneic Stem Cell Transplantation in a Population-Based Setting

The Biological and Clinical Consequences of RNA Splicing Factor U2AF1 Mutation in Myeloid Malignancies

Differential U2AF1 mutation sites, burden and co-mutation genes can predict prognosis in patients with myelodysplastic syndrome

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