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Prognostic and biologic significance of long non-coding RNA profiling in younger adults with cytogenetically normal acute myeloid leukemia
Long non-coding ribonucleic acids (RNAs) are a novel class of RNA molecules, which are increasingly recognized as important molecular players in solid and hematologic malignancies. Herein we investigated whether long non-coding RNA expression is associated with clinical and molecular features, as we...
Autores principales: | , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Ferrata Storti Foundation
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5541873/ https://www.ncbi.nlm.nih.gov/pubmed/28473620 http://dx.doi.org/10.3324/haematol.2017.166215 |
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author | Papaioannou, Dimitrios Nicolet, Deedra Volinia, Stefano Mrózek, Krzysztof Yan, Pearlly Bundschuh, Ralf Carroll, Andrew J. Kohlschmidt, Jessica Blum, William Powell, Bayard L. Uy, Geoffrey L. Kolitz, Jonathan E. Wang, Eunice S. Eisfeld, Ann-Kathrin Orwick, Shelley J. Lucas, David M. Caligiuri, Michael A. Stone, Richard M. Byrd, John C. Garzon, Ramiro Bloomfield, Clara D. |
author_facet | Papaioannou, Dimitrios Nicolet, Deedra Volinia, Stefano Mrózek, Krzysztof Yan, Pearlly Bundschuh, Ralf Carroll, Andrew J. Kohlschmidt, Jessica Blum, William Powell, Bayard L. Uy, Geoffrey L. Kolitz, Jonathan E. Wang, Eunice S. Eisfeld, Ann-Kathrin Orwick, Shelley J. Lucas, David M. Caligiuri, Michael A. Stone, Richard M. Byrd, John C. Garzon, Ramiro Bloomfield, Clara D. |
author_sort | Papaioannou, Dimitrios |
collection | PubMed |
description | Long non-coding ribonucleic acids (RNAs) are a novel class of RNA molecules, which are increasingly recognized as important molecular players in solid and hematologic malignancies. Herein we investigated whether long non-coding RNA expression is associated with clinical and molecular features, as well as outcome of younger adults (aged <60 years) with de novo cytogenetically normal acute myeloid leukemia. Whole transcriptome profiling was performed in a training (n=263) and a validation set (n=114). Using the training set, we identified 24 long non-coding RNAs associated with event-free survival. Linear combination of the weighted expression values of these transcripts yielded a prognostic score. In the validation set, patients with high scores had shorter disease-free (P<0.001), overall (P=0.002) and event-free survival (P<0.001) than patients with low scores. In multivariable analyses, long non-coding RNA score status was an independent prognostic marker for disease-free (P=0.01) and event-free survival (P=0.002), and showed a trend for overall survival (P=0.06). Among multiple molecular alterations tested, which are prognostic in cytogenetically normal acute myeloid leukemia, only double CEBPA mutations, NPM1 mutations and FLT3-ITD associated with distinct long non-coding RNA signatures. Correlation of the long non-coding RNA scores with messenger RNA and microRNA expression identified enrichment of genes involved in lymphocyte/leukocyte activation, inflammation and apoptosis in patients with high scores. We conclude that long non-coding RNA profiling provides meaningful prognostic information in younger adults with cytogenetically normal acute myeloid leukemia. In addition, expression of prognostic long non-coding RNAs associates with oncogenic molecular pathways in this disease. clinicaltrials.gov Identifier: 00048958 (CALGB-8461), 00899223 (CALGB-9665), and 00900224 (CALGB-20202). |
format | Online Article Text |
id | pubmed-5541873 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Ferrata Storti Foundation |
record_format | MEDLINE/PubMed |
spelling | pubmed-55418732017-08-09 Prognostic and biologic significance of long non-coding RNA profiling in younger adults with cytogenetically normal acute myeloid leukemia Papaioannou, Dimitrios Nicolet, Deedra Volinia, Stefano Mrózek, Krzysztof Yan, Pearlly Bundschuh, Ralf Carroll, Andrew J. Kohlschmidt, Jessica Blum, William Powell, Bayard L. Uy, Geoffrey L. Kolitz, Jonathan E. Wang, Eunice S. Eisfeld, Ann-Kathrin Orwick, Shelley J. Lucas, David M. Caligiuri, Michael A. Stone, Richard M. Byrd, John C. Garzon, Ramiro Bloomfield, Clara D. Haematologica Article Long non-coding ribonucleic acids (RNAs) are a novel class of RNA molecules, which are increasingly recognized as important molecular players in solid and hematologic malignancies. Herein we investigated whether long non-coding RNA expression is associated with clinical and molecular features, as well as outcome of younger adults (aged <60 years) with de novo cytogenetically normal acute myeloid leukemia. Whole transcriptome profiling was performed in a training (n=263) and a validation set (n=114). Using the training set, we identified 24 long non-coding RNAs associated with event-free survival. Linear combination of the weighted expression values of these transcripts yielded a prognostic score. In the validation set, patients with high scores had shorter disease-free (P<0.001), overall (P=0.002) and event-free survival (P<0.001) than patients with low scores. In multivariable analyses, long non-coding RNA score status was an independent prognostic marker for disease-free (P=0.01) and event-free survival (P=0.002), and showed a trend for overall survival (P=0.06). Among multiple molecular alterations tested, which are prognostic in cytogenetically normal acute myeloid leukemia, only double CEBPA mutations, NPM1 mutations and FLT3-ITD associated with distinct long non-coding RNA signatures. Correlation of the long non-coding RNA scores with messenger RNA and microRNA expression identified enrichment of genes involved in lymphocyte/leukocyte activation, inflammation and apoptosis in patients with high scores. We conclude that long non-coding RNA profiling provides meaningful prognostic information in younger adults with cytogenetically normal acute myeloid leukemia. In addition, expression of prognostic long non-coding RNAs associates with oncogenic molecular pathways in this disease. clinicaltrials.gov Identifier: 00048958 (CALGB-8461), 00899223 (CALGB-9665), and 00900224 (CALGB-20202). Ferrata Storti Foundation 2017-08 /pmc/articles/PMC5541873/ /pubmed/28473620 http://dx.doi.org/10.3324/haematol.2017.166215 Text en Copyright© 2017 Ferrata Storti Foundation Material published in Haematologica is covered by copyright. All rights are reserved to the Ferrata Storti Foundation. Use of published material is allowed under the following terms and conditions: https://creativecommons.org/licenses/by-nc/4.0/legalcode. Copies of published material are allowed for personal or internal use. Sharing published material for non-commercial purposes is subject to the following conditions: https://creativecommons.org/licenses/by-nc/4.0/legalcode, sect. 3. Reproducing and sharing published material for commercial purposes is not allowed without permission in writing from the publisher. |
spellingShingle | Article Papaioannou, Dimitrios Nicolet, Deedra Volinia, Stefano Mrózek, Krzysztof Yan, Pearlly Bundschuh, Ralf Carroll, Andrew J. Kohlschmidt, Jessica Blum, William Powell, Bayard L. Uy, Geoffrey L. Kolitz, Jonathan E. Wang, Eunice S. Eisfeld, Ann-Kathrin Orwick, Shelley J. Lucas, David M. Caligiuri, Michael A. Stone, Richard M. Byrd, John C. Garzon, Ramiro Bloomfield, Clara D. Prognostic and biologic significance of long non-coding RNA profiling in younger adults with cytogenetically normal acute myeloid leukemia |
title | Prognostic and biologic significance of long non-coding RNA profiling in younger adults with cytogenetically normal acute myeloid leukemia |
title_full | Prognostic and biologic significance of long non-coding RNA profiling in younger adults with cytogenetically normal acute myeloid leukemia |
title_fullStr | Prognostic and biologic significance of long non-coding RNA profiling in younger adults with cytogenetically normal acute myeloid leukemia |
title_full_unstemmed | Prognostic and biologic significance of long non-coding RNA profiling in younger adults with cytogenetically normal acute myeloid leukemia |
title_short | Prognostic and biologic significance of long non-coding RNA profiling in younger adults with cytogenetically normal acute myeloid leukemia |
title_sort | prognostic and biologic significance of long non-coding rna profiling in younger adults with cytogenetically normal acute myeloid leukemia |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5541873/ https://www.ncbi.nlm.nih.gov/pubmed/28473620 http://dx.doi.org/10.3324/haematol.2017.166215 |
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