E-26 Transformation-specific Related Gene Expression and Outcomes in Cytogenetically Normal Acute Myeloid Leukemia: A Meta-analysis
- Author:
- No author available
- Journal Title:
- Chinese Medical Journal
- Issue:
- 12
- DOI:
- 10.4103/0366-6999.207474
- Key Word:
- Leukemia,Myeloid,Acute;Meta-analysis;Prognosis;Recurrence
Abstract： Background:The E-26 transformation-specific related gene (ERG) is frequently expressed in cytogenetically normal acute myeloid leukemia (CN-AML).Herein,we performed a meta-analysis to investigate the relationship between the prognostic significance of ERG expression and CN-AML.Methods:A systematic review of PubMed database and other search engines were used to identify the studies between January 2005 and November 2016.A total of 667 CN-AML patients were collected from seven published studies.Of the 667 patients underwent intensive chemotherapy,429 had low expression of ERG and 238 had high expression of ERG.Summary odds ratio (OR) and the 95％ confidence interval (CI) for the ERG expression and CN-AML were calculated using fixed-or random-effects models.Heterogeneity was assessed using Chi-squared-based Q-statistic test and F statistics.All statistical analyses were performed using R.3.3.1 software packages (R Foundation for Statistical Computing,Vienna,Austria) and RevMan5.3 (Cochrane Collaboration,Copenhagen,Denmark).Results:Overall,patients with high ERG expression had a worse relapse (OR =2.5127,95％ CI:1.5177-4.1601,P =0.0003) and lower complete remission (OR =0.3495,95％ CI:0.2418-0.5051,P ＜ 0.0001).With regard to the known molecular markers,both internal tandem duplications of the fms-related tyrosine kinase 3 gene (OR =3.8634,95％ CI:1.8285-8.1626,P =0.004) and brain and acute leukemia,cytoplasmic (OR =3.1538,95％ CI:2.0537-4.8432,P ＜ 0.0001) were associated with the ERG expression.In addition,the results showed a statistical significance between French-American-British (FAB) classification subtype (minimally differentiated AML and AML without maturation,OR =4.7902,95％ CI:2.7772-8.2624,P ＜ 0.0001;acute monocytic leukemia,OR =0.2324,95％ CI:0.0899-0.6006,P =0.0026) and ERG expression.Conclusion:High ERG expression might be used as a strong adverse prognostic factor in CN-AML.
- [1]Oikawa T.ETS transcription factors: Possible targets for cancer therapy.[J].2004,95(8).
- [2]Klaus H. Metzeler,Annika Dufour,Tobias Benthaus.ERG Expression Is an Independent Prognostic Factor and Allows Refined Risk Stratification in Cytogenetically Normal Acute Myeloid Leukemia: A Comprehensive Analysis of ERG, MN1, and BAALC Transcript Levels Using Oligonucleotide Microarrays[J].2009,27(30).
- [3]F, McLaughlin,V J, Ludbrook,J, Cox,etc.Combined genomic and antisense analysis reveals that the transcription factor Erg is implicated in endothelial cell differentiation.[J].2001,98.
- [4]Samira, Salek-Ardakani,Gil, Smooha,Jasper, de Boer,etc.ERG is a megakaryocytic oncogene.[J].2009,69.
- [5]R, DerSimonian,N, Laird.Meta-analysis in clinical trials.[J].1986,7(3).
- [6]Tsuneyuki, Oikawa,Toshiyuki, Yamada.Molecular biology of the Ets family of transcription factors.[J].2003,303.
- [7]Mrozek K,Bloomfield CD,Heerema NA.Cytogenetics in acute leukemia.[J].2004,18(2).
- [8]Henley KJ,Ellis S,Kile BT,etc.The transcription factor Erg is essential for definitive hematopoiesis and the function of adult hematopoietic stem cells.[J].2008,9(7).
- [9]Tara K, Gregory,David, Wald,Yichu, Chen,etc.Molecular prognostic markers for adult acute myeloid leukemia with normal cytogenetics.[J].2009,2.
- [10]Konstanze, D?hner,Richard F, Schlenk,Marianne, Habdank,etc.Mutant nucleophosmin (NPM1) predicts favorable prognosis in younger adults with acute myeloid leukemia and normal cytogenetics: interaction with other gene mutations.[J].2005,106.
- [11]Sebastian, Schwind,Guido, Marcucci,Kati, Maharry,etc.BAALC and ERG expression levels are associated with outcome and distinct gene and microRNA expression profiles in older patients with de novo cytogenetically normal acute myeloid leukemia: a Cancer and Leukemia Group B study.[J].2010,116.
- [12]Adam J, Mead,David C, Linch,Robert K, Hills,etc.FLT3 tyrosine kinase domain mutations are biologically distinct from and have a significantly more favorable prognosis than FLT3 internal tandem duplications in patients with acute myeloid leukemia.[J].2007,110.
- [13]P H, Sorensen,S L, Lessnick,D, Lopez-Terrada,etc.A second Ewing's sarcoma translocation, t(21; 22), fuses the EWS gene to another ETS-family transcription factor, ERG.[J].1994,6.
- [14]K?v?lc?m Eren, Erdo?an,Mehmet Ali, Deveci,Zeynep Ruken, Hakkoymaz,etc.Therapy-Induced Neural Differentiation in Ewing's Sarcoma: A Case Report and Review of the Literature.[J].2017,(Spec ).
- [15]Duval S,Tweedie R.Trim and fill: A simple funnel-plot-based method of testing and adjusting for publication bias in meta-analysis.[J].2000,56(2).
- [16]Ehninger G,Thiel E,Bloomfield CD,etc.BAALC expression and FLT3 internal tandem duplication mutations in acute myeloid leukemia patients with normal cytogenetics: prognostic implications.[J].2006,24(5).
- [17]Claudia D, Baldus,Stephan M, Tanner,Amy S, Ruppert,etc.BAALC expression predicts clinical outcome of de novo acute myeloid leukemia patients with normal cytogenetics: a Cancer and Leukemia Group B Study.[J].2003,102.
- [18]Fleischmann, Maximilian,Schnetzke, Ulf,Schrenk, Karin G.,etc.Outcome of FLT3-ITD-positive acute myeloid leukemia: impact of allogeneic stem cell transplantation and tyrosine kinase inhibitor treatment[J].2017,143(2).
- [19]Dohner K,Frohling S,Schlenk RF,etc.Prognostic significance of partial tandem duplications of the MLL gene in adult patients 16 to 60 years old with acute myeloid leukemia and normal cytogenetics: a study of the Acute Myeloid Leukemia Study Group Ulm.[J].2002,20(15).
- [20]K F, Tse,G, Mukherjee,D, Small.Constitutive activation of FLT3 stimulates multiple intracellular signal transducers and results in transformation.[J].2000,14(10).
- [21]Scott A, Tomlins,Daniel R, Rhodes,Sven, Perner,etc.Recurrent fusion of TMPRSS2 and ETS transcription factor genes in prostate cancer.[J].2005,310.
- [22]Salah, Aref,Tawfik, Al Khodary,Tarek Abou, Zeed,etc.The Prognostic Relevance of BAALC and ERG Expression Levels in Cytogenetically Normal Pediatric Acute Myeloid Leukemia.[J].2015,31(1).
- [23]Egger M.,Smith G. D.,Schneider M.,etc.Bias in meta-analysis detected by a simple, graphical test[J].1997.
- [24]Attia M,Farrag W,Elahwal L,etc.BAALC and ERG expression in acute myeloid leukemia with normal karyotype: impact on prognosis.[J].2010,32(2).
- [25]Ley,T.J.,Miller,C.,Ding,L.,etc.Genomic and epigenomic landscapes of adult de novo acute myeloid leukemia[J].2013,368(22).
- [26]Rebechi, Melanie T.,Pratz, Keith W..Genomic instability is a principle pathologic feature of FLT3 ITD kinase activity in acute myeloid leukemia leading to clonal evolution and disease progression.[J].2017,58(9).
- [27]Christian, Langer,Michael D, Radmacher,Amy S, Ruppert,etc.High BAALC expression associates with other molecular prognostic markers, poor outcome, and a distinct gene-expression signature in cytogenetically normal patients younger than 60 years with acute myeloid leukemia: a Cancer and Leukemia Group B (CALGB) st[J].2008,111.