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Prognostic DNA Methylation Patterns in Cytogenetically Normal Acute Myeloid Leukemia are predefined by Stem Cell Chromatin Marks [gene expression]

ABSTRACT: GEP of 10 diagnostic bone marrow samples of CN-AML used to correlate promoter DNA methylation to mRNA levels.

ORGANISM(S): Homo sapiens

PROVIDER: GSE31941 | GEO | 2011/09/07

SECONDARY ACCESSION(S): PRJNA155299

REPOSITORIES: GEO

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Prognostic DNA Methylation Patterns in Cytogenetically Normal Acute Myeloid Leukemia are predefined by Stem Cell Chromatin Marks

Project description:GEP of 10 diagnostic bone marrow samples of CN-AML used to correlate promoter DNA methylation to mRNA levels. Ficoll separated MNC

2011-09-06 | E-GEOD-31941 | biostudies-arrayexpress

Prognostic DNA Methylation Patterns in Cytogenetically Normal Acute Myeloid Leukemia are predefined by Stem Cell Chromatin Marks [methylation]

Project description:Cytogenetically normal acute myeloid leukemia (CN-AML) comprise between forty and fifty percent of all adult acute myeloid leukemia (AML) cases. In this clinically diverse group molecular aberrations such as FLT3ITD, NPM1 and CEBPA mutations recently have added to the prognostic accuracy. Aberrant DNA methylation is a hallmark of cancer including AML. We investigated in total 89 CN-AML samples in a test and a validation cohort for genome-wide promoter DNA methylation with Illumina Methylation Bead arrays and compared them to normal myeloid precursors and global gene expression. IDH and NPM1 mutations were associated with different methylation patterns (p=0.0004 and 0.04, respectively). Genome-wide methylation levels were elevated in IDH mutated samples (p=0.006). We observed a negative impact of DNA methylation on transcription. Genes targeted by Polycomb group (PcG) proteins and genes associated with bivalent histone marks in stem cells showed increased aberrant methylation in AML (p<0.0001). Furthermore, high methylation levels of PcG target genes were independently associated with better progression free (OR 0.47, p=0.01) and overall survival (OR 0.36, p=0.001). In summary, genome wide methylation patterns show preferential methylation of PcG targets with prognostic impact in CN-AML.

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Prognostic DNA Methylation Patterns in Cytogenetically Normal Acute Myeloid Leukemia are predefined by Stem Cell Chromatin Marks [methylation]

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Co-expression of microrna and mrna in cytogenetically normal acute myeloid leukemia patients [miRNA]

Project description:The study integrated both miRNA and mRNA profiles to explore novel miRNA-mRNA interactions that affect the regulatory patterns in de novo CN-AML. A total of 637 significant negative correlations (FDR <0.05) were reported. Network analysis revealed a cluster of 12 miRNAs that represents the majority of the mRNA targets. Within the cluster, five miRNAs; miR-495-3p, miR-185-5p, let-7i-5p, miR-409-3p, and miR-127-3p were suggested to play a pivotal role in the regulation of CN-AML as they are associated with negative regulation of myeloid leukocyte differentiation, negative regulation of myeloid cell differentiation, positive regulation of haematopoiesis, and hematopoiesis and its regulation. Three novel interactions in CN-AML were predicted, let-7i-5p:HOXA9, miR-495-3p:PIK3R1 and miR-495-3p:CDK6 which are responsible in regulating myeloid cell differentiation in CN-AML.

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Co-expression of microrna and mrna in cytogenetically normal acute myeloid leukemia patients [mRNA]

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Molecular prognostic factors in cytogenetically normal acute myeloid leukemia.

Project description: Not available

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Gene expression profiles of mono- and biallelic CEBPA mutations in cytogenetically normal AML

Project description:Purpose: CEBPA mutations are found as either biallelic (biCEBPA) or monoallelic (moCEBPA). We set out to explore whether the kind of CEBPA mutation is of prognostic relevance in cytogenetically normal AML (CN-AML). Patients and Methods: 467 homogeneously treated CN-AML patients were subdivided into moCEBPA, biCEBPA and wildtype (wt) CEBPA patients. The subgroups were analyzed for clinical parameters and for additional mutations in the NPM1, FLT3 and MLL genes. Furthermore, we obtained gene expression profiles (GEP) for a subgroup of 61 patients using oligonucleotide microarrays. 61 bone-marrow samples from CN-AML patients were analyzed using Affymetrix HG-U133 oligonucleotide microarrays (Affymetrix, Santa Clara, CA). Sample preparation, hybridization and image acquisition were performed according to standard Affymetrix protocols. Custom chip definition files based on the GeneAnnot database were used for data analysis (Ferrari et al, BMC Bioinformatics 8:446). The twilight algorithm was used to comapre gene expression profiles of patients with wildtype CEBPA and mono- and biallelic CEBPA mutations.

2010-05-16 | E-GEOD-15210 | biostudies-arrayexpress

Prognostic and Biologic Relevance of Clinically Applicable Long Non-Coding RNA Profiling in Older Patients with Cytogenetically Normal AML

Project description:We have previously shown that expression levels of 48 long non-coding RNAs (lncRNAs) can generate a prognostic lncRNA score that independently associates with outcome of older patients (aged ≥ 60 years) with cytogenetically normal acute myeloid leukemia (CN-AML). However, the techniques that were used to identify and measure prognostic lncRNAs are not tailored for real-life clinical testing. Herein we report on an assay (based on the nCounter platform), which is designed to produce targeted measurements of prognostic lncRNAs in a clinically friendly manner. We analyzed an independent cohort of 76 older CN-AML patients and found that the nCounter assay yielded reproducible measurements and that the lncRNA score retained its prognostic value; patients with favorable lncRNA scores were more likely to achieve a complete remission (CR, P=0.009) and have longer diseased-free (DFS, P=0.05), overall (OS, P=0.02) and event-free survival (EFS, P=0.002) than patients with unfavorable lncRNA scores. In multivariable analyses, lncRNA score status independently associated with CR rates (P=0.02), as well as OS (P=0.02) and EFS (P=0.02) duration. To gain biological insights, we examined a dataset of older CN-AML patients, previously analyzed with RNA sequencing. We found genes involved in immune response and B cell receptor signaling (for which targeted inhibitors are currently available) to be enriched in patients with unfavorable lncRNA scores. We conclude that clinically applicable lncRNA profiling is feasible and potentially useful for risk stratification of older CN-AML patients. In addition we identify potentially targetable molecular pathways that are active in the high-risk patients with unfavorable lncRNA scores.

2019-05-09 | GSE130923 | GEO

The Prognostic Significance of PDE7B in Cytogenetically Normal Acute Myeloid Leukemia.

Project description: Not available

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