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Transcription profiling by array of older patients with cytogenetically normal AML with high or low BAALC- and ERG-related gene-expression signatures

ABSTRACT: Gene expression microarray data for analysis of BAALC- and ERG-related gene-expression signatures in older patients with cytogenetically normal AML. Summary measures of the expression levels were computed for each probe set using the robust multichip average method, which incorporates quantile normalization of arrays (Irizarry et al., 2003). The RMA data has not been submitted to ArrayExpress.

ORGANISM(S): Homo sapiens

SUBMITTER: Guido Marcucci

PROVIDER: E-TABM-1072 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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MicroRNA profiling by array of older patients with cytogenetically normal AML with high or low BAALC- and ERG-related gene-expression signatures

Project description:microRNA expression microarray data for analysis of BAALC- and ERG-related miR-expression signatures in older patients with cytogenetically normal AML. The signal intensity was calculated for each spot making an adjustment for local background (i.e., mean foreground minus the median background). Signal intensities less than one were set equal to one and then log-transformed. Log-intensities from replicate spots were averaged. Quantile normalization was performed on arrays using all human and mouse microRNA probes represented on the array. For each microRNA probe, an adjustment was made for batch effects (ie, differences in expression related to the batch in which arrays were hybridized). The normalized data has not been submitted to ArrayExpress.

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Project description:Recently, deep sequencing of melanoma and pediatric acute lymphoblastic leukemia samples identified a new microRNA - miR-3151 - embedded in intron 1 of the BAALC gene. MiR genes are located throughout the genome, but about one-third of mammalian miRs reside within introns of host genes. Some of these intronic miRs have been found to act in functional synergism with their host genes. These findings led us to hypothesize that miR-3151 could be overexpressed in patients with elevated BAALC levels and thus might contribute to the adverse prognostic impact of its host gene, either acting in concert with BAALC or perhaps even being the element predominantly responsible for the adverse outcome observed in BAALC overexpressing AML patients.Thus, we have measured miR-151 and BAALC expression in a cohort of molecularly well characterized de novo CN-AML patients to assess the impact of miR-3151 expression alone and in combination with its host BAALC on outcome. microRNA expression profiles associated with miR-3151 expression in older patients with cytogenetically normal acute myeloid leukemia were derived using microarrays. The corresponding affymetrix data can be found under accession number E-MTAB-1075.

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miR-3151 interplays with its host gene BAALC and independently impacts on outcome of patients with cytogenetically normal acute myeloid leukemia - expression microarray data

Project description:Recently, deep sequencing of melanoma and pediatric acute lymphoblastic leukemia samples identified a new microRNA - miR-3151 - embedded in intron 1 of the BAALC gene. MiR genes are located throughout the genome, but about one-third of mammalian miRs reside within introns of host genes. Some of these intronic miRs have been found to act in functional synergism with their host genes. These findings led us to hypothesize that miR-3151 could be overexpressed in patients with elevated BAALC levels and thus might contribute to the adverse prognostic impact of its host gene, either acting in concert with BAALC or perhaps even being the element predominantly responsible for the adverse outcome observed in BAALC overexpressing AML patients.Thus, we have measured miR-3151 and BAALC expression in a cohort of molecularly well characterized de novo CN-AML patients to assess the impact of miR-3151 expression alone and in combination with its host BAALC on outcome. microRNA expression profiles associated with miR-3151 expression in older patients with cytogenetically normal acute myeloid leukemia were derived using microarrays. The corresponding microRNA expression data can be found under accession number E-MTAB-1074.

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Project description:BAALC and ERG expression levels are prognostic markers in younger (< 60 years) cytogenetically normal acute myeloid leukemia (CN-AML) adults; their prognostic impact in older (? 60 years) patients requires further investigation. We evaluated pretreatment expression of BAALC and ERG in 158 de novo patients treated on cytarabine/daunorubicin-based protocols. The patients were also characterized for other established molecular prognosticators. Low BAALC and ERG expression levels were associated with better outcome in univariable and multivariable analyses. Expression levels of both BAALC and ERG were the only factors significantly associated with overall survival upon multivariable analysis. To gain biological insights, we derived gene expression signatures associated with BAALC and ERG expression in older CN-AML patients. Furthermore, we derived the first microRNA expression signatures associated with the expression of these 2 genes. In low BAALC expressers, genes associated with undifferentiated hematopoietic precursors and unfavorable outcome predictors were down-regulated, whereas HOX genes and HOX-gene-embedded microRNAs were up-regulated. Low ERG expressers presented with down-regulation of genes involved in the DNA-methylation machinery, and up-regulation of miR-148a, which targets DNMT3B. We conclude that in older CN-AML patients, low BAALC and ERG expression associates with better outcome and distinct gene and microRNA expression signatures that could aid in identifying new targets and novel therapeutic strategies for older patients.

| S-EPMC3031412 | biostudies-literature

Gene-expression profiling according to MN1 mRNA expression levels in de novo cytogenetically normal acute myeloid leukemia patients aged 60 years or older.

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2011-10-20 | E-TABM-1189 | biostudies-arrayexpress

microRNA-expression profiling according to MN1 mRNA expression levels in de novo cytogenetically normal acute myeloid leukemia patients aged 60 years or older.

Project description:microRNA-expression profiling according to MN1 mRNA expression levels in de novo cytogenetically normal acute myeloid leukemia patients aged 60 years or older.

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RNA-seq of CN, CN/AML, and CN/AML BAALC KO iPSCs-derived HSPCs

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2021-03-08 | E-MTAB-10162 | 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

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