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The long noncoding RNA, treRNA, decreases DNA damage and is associated with poor response to chemotherapy in chronic lymphocytic leukemia

The study of long noncoding RNAs (lncRNAs) is an emerging area of cancer research, in part due to their ability to serve as disease biomarkers. However, few studies have investigated lncRNAs in chronic lymphocytic leukemia (CLL). We have identified one particular lncRNA, treRNA, which is overexpress...

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Autores principales: Miller, Cecelia R., Ruppert, Amy S., Fobare, Sydney, Chen, Timothy L., Liu, Chaomei, Lehman, Amy, Blachly, James S., Zhang, Xiaoli, Lucas, David M., Grever, Michael R., Tallman, Martin S., Flinn, Ian W., Rassenti, Laura Z., Kipps, Thomas J., Sampath, Deepa, Coombes, Kevin R., Hertlein, Erin K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5432228/
https://www.ncbi.nlm.nih.gov/pubmed/28412730
http://dx.doi.org/10.18632/oncotarget.15401
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author Miller, Cecelia R.
Ruppert, Amy S.
Fobare, Sydney
Chen, Timothy L.
Liu, Chaomei
Lehman, Amy
Blachly, James S.
Zhang, Xiaoli
Lucas, David M.
Grever, Michael R.
Tallman, Martin S.
Flinn, Ian W.
Rassenti, Laura Z.
Kipps, Thomas J.
Sampath, Deepa
Coombes, Kevin R.
Hertlein, Erin K.
author_facet Miller, Cecelia R.
Ruppert, Amy S.
Fobare, Sydney
Chen, Timothy L.
Liu, Chaomei
Lehman, Amy
Blachly, James S.
Zhang, Xiaoli
Lucas, David M.
Grever, Michael R.
Tallman, Martin S.
Flinn, Ian W.
Rassenti, Laura Z.
Kipps, Thomas J.
Sampath, Deepa
Coombes, Kevin R.
Hertlein, Erin K.
author_sort Miller, Cecelia R.
collection PubMed
description The study of long noncoding RNAs (lncRNAs) is an emerging area of cancer research, in part due to their ability to serve as disease biomarkers. However, few studies have investigated lncRNAs in chronic lymphocytic leukemia (CLL). We have identified one particular lncRNA, treRNA, which is overexpressed in CLL B-cells. We measured transcript expression in 144 CLL patient samples and separated samples into high or low expression of treRNA relative to the overall median. We found that high expression of treRNA is significantly associated with shorter time to treatment. High treRNA also correlates with poor prognostic indicators such as unmutated IGHV and high ZAP70 protein expression. We validated these initial findings in samples collected in a clinical trial comparing the nucleoside analog fludarabine alone or in combination with the alkylating agent cyclophosphamide in untreated CLL samples collected prior to starting therapy (E2997). High expression of treRNA was independently prognostic for shorter progression free survival in patients receiving fludarabine plus cyclophosphamide. Given these results, in order to study the role of treRNA in DNA damage response we generated a model cell line system where treRNA was over-expressed in the human B-CLL cell line OSU-CLL. Relative to the vector control line, there was less cell death in OSU-CLL over-expressing treRNA after exposure to fludarabine and mafosfamide, due in part to a reduction in DNA damage. Therefore, we suggest that treRNA is a novel biomarker in CLL associated with aggressive disease and poor response to chemotherapy through enhanced protection against cytotoxic mediated DNA damage.
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spelling pubmed-54322282017-05-17 The long noncoding RNA, treRNA, decreases DNA damage and is associated with poor response to chemotherapy in chronic lymphocytic leukemia Miller, Cecelia R. Ruppert, Amy S. Fobare, Sydney Chen, Timothy L. Liu, Chaomei Lehman, Amy Blachly, James S. Zhang, Xiaoli Lucas, David M. Grever, Michael R. Tallman, Martin S. Flinn, Ian W. Rassenti, Laura Z. Kipps, Thomas J. Sampath, Deepa Coombes, Kevin R. Hertlein, Erin K. Oncotarget Research Paper The study of long noncoding RNAs (lncRNAs) is an emerging area of cancer research, in part due to their ability to serve as disease biomarkers. However, few studies have investigated lncRNAs in chronic lymphocytic leukemia (CLL). We have identified one particular lncRNA, treRNA, which is overexpressed in CLL B-cells. We measured transcript expression in 144 CLL patient samples and separated samples into high or low expression of treRNA relative to the overall median. We found that high expression of treRNA is significantly associated with shorter time to treatment. High treRNA also correlates with poor prognostic indicators such as unmutated IGHV and high ZAP70 protein expression. We validated these initial findings in samples collected in a clinical trial comparing the nucleoside analog fludarabine alone or in combination with the alkylating agent cyclophosphamide in untreated CLL samples collected prior to starting therapy (E2997). High expression of treRNA was independently prognostic for shorter progression free survival in patients receiving fludarabine plus cyclophosphamide. Given these results, in order to study the role of treRNA in DNA damage response we generated a model cell line system where treRNA was over-expressed in the human B-CLL cell line OSU-CLL. Relative to the vector control line, there was less cell death in OSU-CLL over-expressing treRNA after exposure to fludarabine and mafosfamide, due in part to a reduction in DNA damage. Therefore, we suggest that treRNA is a novel biomarker in CLL associated with aggressive disease and poor response to chemotherapy through enhanced protection against cytotoxic mediated DNA damage. Impact Journals LLC 2017-02-16 /pmc/articles/PMC5432228/ /pubmed/28412730 http://dx.doi.org/10.18632/oncotarget.15401 Text en Copyright: © 2017 Miller et al. http://creativecommons.org/licenses/by/3.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) (CC-BY), which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Research Paper
Miller, Cecelia R.
Ruppert, Amy S.
Fobare, Sydney
Chen, Timothy L.
Liu, Chaomei
Lehman, Amy
Blachly, James S.
Zhang, Xiaoli
Lucas, David M.
Grever, Michael R.
Tallman, Martin S.
Flinn, Ian W.
Rassenti, Laura Z.
Kipps, Thomas J.
Sampath, Deepa
Coombes, Kevin R.
Hertlein, Erin K.
The long noncoding RNA, treRNA, decreases DNA damage and is associated with poor response to chemotherapy in chronic lymphocytic leukemia
title The long noncoding RNA, treRNA, decreases DNA damage and is associated with poor response to chemotherapy in chronic lymphocytic leukemia
title_full The long noncoding RNA, treRNA, decreases DNA damage and is associated with poor response to chemotherapy in chronic lymphocytic leukemia
title_fullStr The long noncoding RNA, treRNA, decreases DNA damage and is associated with poor response to chemotherapy in chronic lymphocytic leukemia
title_full_unstemmed The long noncoding RNA, treRNA, decreases DNA damage and is associated with poor response to chemotherapy in chronic lymphocytic leukemia
title_short The long noncoding RNA, treRNA, decreases DNA damage and is associated with poor response to chemotherapy in chronic lymphocytic leukemia
title_sort long noncoding rna, trerna, decreases dna damage and is associated with poor response to chemotherapy in chronic lymphocytic leukemia
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5432228/
https://www.ncbi.nlm.nih.gov/pubmed/28412730
http://dx.doi.org/10.18632/oncotarget.15401
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