Dynamic and extensive A-to-I RNA recoding in immunoglobulin shapes myeloid neoplasm transcriptome

Functional adenosine-to-inosine mRNA editing sites are continuously identified in cellular organisms. Despite that several editing sites have been linked to various human cancers, the dynamic RNA editing in the progression of myeloid neoplasms remains less known, preventing a clearer understanding of the functional repertoire of RNA editing in blood diseases. By analyzing transcriptomes from healthy controls, low-risk myelodysplastic syndrome, high-risk myelodysplastic syndrome, and acute myeloid leukemia, we reveal widespread and dynamic RNA editing events accompanying disease progression. Immunoglobulin genes are enriched for nonsynonymous editing sites with significantly altered editing levels in myeloid neoplasms, and such recoding sites often show genomic substitutions to hardwired G during mammalian evolution. Collectively, our findings broaden the functional spectrum of RNA editing in human and highlight its potential as a driver, responsor, or biomarker of myeloid neoplasms, underscoring its significance in human disease evolution.