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Expression levels of long non-coding RNAs are prognostic for AML outcome

BACKGROUND: Long non-coding RNA (lncRNA) expression has been implicated in a range of molecular mechanisms that are central in cancer. However, lncRNA expression has not yet been comprehensively characterized in acute myeloid leukemia (AML). Here, we assess to what extent lncRNA expression is progno...

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Autores principales: Mer, Arvind Singh, Lindberg, Johan, Nilsson, Christer, Klevebring, Daniel, Wang, Mei, Grönberg, Henrik, Lehmann, Soren, Rantalainen, Mattias
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5889529/
https://www.ncbi.nlm.nih.gov/pubmed/29625580
http://dx.doi.org/10.1186/s13045-018-0596-2
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author Mer, Arvind Singh
Lindberg, Johan
Nilsson, Christer
Klevebring, Daniel
Wang, Mei
Grönberg, Henrik
Lehmann, Soren
Rantalainen, Mattias
author_facet Mer, Arvind Singh
Lindberg, Johan
Nilsson, Christer
Klevebring, Daniel
Wang, Mei
Grönberg, Henrik
Lehmann, Soren
Rantalainen, Mattias
author_sort Mer, Arvind Singh
collection PubMed
description BACKGROUND: Long non-coding RNA (lncRNA) expression has been implicated in a range of molecular mechanisms that are central in cancer. However, lncRNA expression has not yet been comprehensively characterized in acute myeloid leukemia (AML). Here, we assess to what extent lncRNA expression is prognostic of AML patient overall survival (OS) and determine if there are indications of lncRNA-based molecular subtypes of AML. METHODS: We performed RNA sequencing of 274 intensively treated AML patients in a Swedish cohort and quantified lncRNA expression. Univariate and multivariate time-to-event analysis was applied to determine association between individual lncRNAs with OS. Unsupervised statistical learning was applied to ascertain if lncRNA-based molecular subtypes exist and are prognostic. RESULTS: Thirty-three individual lncRNAs were found to be associated with OS (adjusted p value < 0.05). We established four distinct molecular subtypes based on lncRNA expression using a consensus clustering approach. LncRNA-based subtypes were found to stratify patients into groups with prognostic information (p value < 0.05). Subsequently, lncRNA expression-based subtypes were validated in an independent patient cohort (TCGA-AML). LncRNA subtypes could not be directly explained by any of the recurrent cytogenetic or mutational aberrations, although associations with some of the established genetic and clinical factors were found, including mutations in NPM1, TP53, and FLT3. CONCLUSION: LncRNA expression-based four subtypes, discovered in this study, are reproducible and can effectively stratify AML patients. LncRNA expression profiling can provide valuable information for improved risk stratification of AML patients. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13045-018-0596-2) contains supplementary material, which is available to authorized users.
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spelling pubmed-58895292018-04-10 Expression levels of long non-coding RNAs are prognostic for AML outcome Mer, Arvind Singh Lindberg, Johan Nilsson, Christer Klevebring, Daniel Wang, Mei Grönberg, Henrik Lehmann, Soren Rantalainen, Mattias J Hematol Oncol Research BACKGROUND: Long non-coding RNA (lncRNA) expression has been implicated in a range of molecular mechanisms that are central in cancer. However, lncRNA expression has not yet been comprehensively characterized in acute myeloid leukemia (AML). Here, we assess to what extent lncRNA expression is prognostic of AML patient overall survival (OS) and determine if there are indications of lncRNA-based molecular subtypes of AML. METHODS: We performed RNA sequencing of 274 intensively treated AML patients in a Swedish cohort and quantified lncRNA expression. Univariate and multivariate time-to-event analysis was applied to determine association between individual lncRNAs with OS. Unsupervised statistical learning was applied to ascertain if lncRNA-based molecular subtypes exist and are prognostic. RESULTS: Thirty-three individual lncRNAs were found to be associated with OS (adjusted p value < 0.05). We established four distinct molecular subtypes based on lncRNA expression using a consensus clustering approach. LncRNA-based subtypes were found to stratify patients into groups with prognostic information (p value < 0.05). Subsequently, lncRNA expression-based subtypes were validated in an independent patient cohort (TCGA-AML). LncRNA subtypes could not be directly explained by any of the recurrent cytogenetic or mutational aberrations, although associations with some of the established genetic and clinical factors were found, including mutations in NPM1, TP53, and FLT3. CONCLUSION: LncRNA expression-based four subtypes, discovered in this study, are reproducible and can effectively stratify AML patients. LncRNA expression profiling can provide valuable information for improved risk stratification of AML patients. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13045-018-0596-2) contains supplementary material, which is available to authorized users. BioMed Central 2018-04-07 /pmc/articles/PMC5889529/ /pubmed/29625580 http://dx.doi.org/10.1186/s13045-018-0596-2 Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Mer, Arvind Singh
Lindberg, Johan
Nilsson, Christer
Klevebring, Daniel
Wang, Mei
Grönberg, Henrik
Lehmann, Soren
Rantalainen, Mattias
Expression levels of long non-coding RNAs are prognostic for AML outcome
title Expression levels of long non-coding RNAs are prognostic for AML outcome
title_full Expression levels of long non-coding RNAs are prognostic for AML outcome
title_fullStr Expression levels of long non-coding RNAs are prognostic for AML outcome
title_full_unstemmed Expression levels of long non-coding RNAs are prognostic for AML outcome
title_short Expression levels of long non-coding RNAs are prognostic for AML outcome
title_sort expression levels of long non-coding rnas are prognostic for aml outcome
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5889529/
https://www.ncbi.nlm.nih.gov/pubmed/29625580
http://dx.doi.org/10.1186/s13045-018-0596-2
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