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RNA editing contributes to epitranscriptome diversity in chronic lymphocytic leukemia

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Gassner, Franz, Zaborsky, Nadja, Buchumenski, Ilana, Levanon, Erez, Gatterbauer, Matthias, Schubert, Maria, Rauscher, Stefanie, Hebenstreit, Daniel, Nadeu, Ferran, Campo, Elias, Egle, Alexander, Greil, Richard and Geisberger, Roland (2021) RNA editing contributes to epitranscriptome diversity in chronic lymphocytic leukemia. Leukemia, 35 . pp. 1053-1063. doi:10.1038/s41375-020-0995-6

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Official URL: https://doi.org/10.1038/s41375-020-0995-6

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Abstract

RNA editing—primarily conversion of adenosine to inosine (A > I)—is a widespread posttranscriptional mechanism, mediated by Adenosine Deaminases acting on RNA (ADAR) enzymes to alter the RNA sequence of primary transcripts. Hence, in addition to somatic mutations and alternative RNA splicing, RNA editing can be a further source for recoding events. Although RNA editing has been detected in many solid cancers and normal tissue, RNA editing in chronic lymphocytic leukemia (CLL) has not been addressed so far. We determined global RNA editing and recurrent, recoding RNA editing events from matched RNA-sequencing and whole exome sequencing data in CLL samples from 45 untreated patients. RNA editing was verified in a validation cohort of 98 CLL patients and revealed substantially altered RNA editing profiles in CLL compared with normal B cells. We further found that RNA editing patterns were prognostically relevant. Finally, we showed that ADAR knockout decreased steady state viability of MEC1 cells and made them more susceptible to treatment with fludarabine and ibrutinib in vitro. We propose that RNA editing contributes to the pathophysiology of CLL and targeting the RNA editing machinery could be a future strategy to maximize treatment efficacy.

Item Type: Journal Article
Subjects: Q Science > QH Natural history > QH426 Genetics
R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Divisions: Faculty of Science > Life Sciences (2010- )
Library of Congress Subject Headings (LCSH): RNA editing, Genetic regulation, Chronic lymphocytic leukemia
Journal or Publication Title: Leukemia
Publisher: Nature Publishing Group
ISSN: 0887-6924
Official Date: April 2021
Dates:
DateEvent
April 2021Published
30 July 2020Available
21 July 2020Accepted
Volume: 35
Page Range: pp. 1053-1063
DOI: 10.1038/s41375-020-0995-6
Status: Peer Reviewed
Publication Status: Published
Access rights to Published version: Open Access
RIOXX Funder/Project Grant:
Project/Grant IDRIOXX Funder NameFunder ID
P28201Austrian Science Fundhttp://dx.doi.org/10.13039/501100002428
PMP15/00007Instituto de Salud Carlos IIIhttp://dx.doi.org/10.13039/501100004587
HR17-00221“la Caixa” FoundationUNSPECIFIED
BES-2016-076372Ministerio de Economía y CompetitividadUNSPECIFIED
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