EZH2 dysregulation: Potential biomarkers predicting prognosis and guiding treatment choice in acute myeloid leukaemia

Abstract

Accumulating studies have proved EZH2 dysregulation mediated by mutation and expression in diverse human cancers including AML. However, the expression pattern of EZH2 remains controversial in acute myeloid leukaemia (AML). EZH1/2 expression and mutation were analysed in 200 patients with AML. EZH2 expression was significantly decreased in AML patients compared with normal controls but not for EZH1 expression. EZH2 mutation was identified three of the 200 AML patients (1.5%, 3/200), whereas none of the patients harboured EZH1 mutation (0%, 0/200).EZH2 expression and mutation were significantly associated with −7/del(7) karyotypes. Moreover, lower EZH2 expression was associated with older age, higher white blood cells, NPM1 mutation, CEBPA wild-type and WT1 wild-type. Patients with EZH2 mutation showed shorter overall survival (OS) and leukaemia-free survival (LFS) than patients without EHZ2 mutation after receiving autologous or allogeneic haematopoietic stem cell transplantation (HSCT). However, EZH2 expression has no effect on OS and LFS of AML patients. Notably, in EZH2 low group, patients undergone HSCT had significantly better OS and LFS compared with patients only received chemotherapy, whereas no significant difference was found in OS and LFS between chemotherapy and HSCT patients in EZH2 high group. Collectively, EZH2 dysregulation caused by mutation and under-expression identifies specific subtypes of AML EZH2 dysregulation may be acted as potential biomarkers predicting prognosis and guiding the treatment choice between transplantation and chemotherapy. K E Y W O R D SAML, expression, EZH1, EZH2, mutation | 1641 CHU et al.

Identification and validation of obesity-related gene LEP methylation as a prognostic indicator in patients with acute myeloid leukemia

“…Differential expression analysis for RNA/miRNA sequencing data was calculated using the raw read counts with the R/Bioconductor package “edgeR”, all analyses were controlled for the false discovery rate (FDR) by the Benjamini–Hochberg procedure [ 24 ]. The miRNA which could target LEP was identified by the venn analysis ( http://bioinformatics.psb.ugent.be/webtools/Venn/ ) of three websites miRDB ( http://mirdb.org/miRDB/ ), miRWalk ( http://mirwalk.umm.uni-heidelberg.de/ ) and TargetScan ( http://www.targetscan.org/vert_72/ ) [ 25 , 26 ]. All basic statistical analyses were performed using the base functions in R version 3.4 ( https://www.r-project.org ).…”

Distinct associations of NEDD4L expression with genetic abnormalities and prognosis in acute myeloid leukemia

“…5 a, b and Additional file 3 : Table S2). The top 50 upregulated genes including CDH1 and the top 50 downregulated genes such as H19 were significantly associated with prognosis in AML by our previous studies [ 29 , 30 ]. In addition, the GO (Gene Ontology) analysis demonstrated that these DEGs involved in biologic processes, including multicellular organismal process, system development, multicellular organism development, and biological adhesion (Fig.…”

Deregulated Gene Expression Profiles and Regulatory Networks in Adult and Pediatric RUNX1/RUNX1T1-Positive AML Patients

“…What is more, our findings regarding the deregulated expression of EZH2 in AML agree with previous reports, suggesting that its overexpression (apart from mutation) promotes cell proliferation in hematologic and other malignancies. EZH2 controls the expression of genes involved in stem cell maintenance and differentiation and its down-regulation inhibits apoptosis, affects the expression of MAD2 and CDC20, and promotes chromosomal instability in AML cells [ 87 , 88 , 89 , 90 , 91 , 92 ]. Our findings also highlight the deregulated expression of SUZ12, another component of PRC2, responsible for the transcriptional repression of genes via methylation [ 93 , 94 ].…”