RNA editing contributes to epitranscriptome diversity in chronic lymphocytic leukemia

Leukemia. 2021 Apr;35(4):1053-1063. doi: 10.1038/s41375-020-0995-6. Epub 2020 Jul 30.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Deaminase / genetics
  • Adult
  • Aged
  • Aged, 80 and over
  • Alu Elements
  • Cell Line, Tumor
  • Chromosome Aberrations
  • Epigenesis, Genetic*
  • Female
  • Gene Expression Profiling*
  • Gene Expression Regulation, Leukemic*
  • Humans
  • Immunoglobulin Heavy Chains / genetics
  • In Situ Hybridization, Fluorescence
  • Leukemia, Lymphocytic, Chronic, B-Cell / diagnosis
  • Leukemia, Lymphocytic, Chronic, B-Cell / genetics*
  • Leukemia, Lymphocytic, Chronic, B-Cell / therapy
  • Male
  • Middle Aged
  • Mutation
  • Neoplasm Staging
  • Open Reading Frames
  • RNA Editing*
  • RNA-Binding Proteins / genetics
  • Transcriptome*


  • Immunoglobulin Heavy Chains
  • RNA-Binding Proteins
  • ADAR protein, human
  • Adenosine Deaminase