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Please use this identifier to cite or link to this item: https://hdl.handle.net/2445/214988
Detection of early seeding of Richter transformation in chronic lymphocytic leukemia
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Richter transformation (RT) is a paradigmatic evolution of chronic lymphocytic leukemia (CLL) into a very aggressive large B cell lymphoma conferring a dismal prognosis. The mechanisms driving RT remain largely unknown. We characterized the whole genome, epigenome and transcriptome, combined with single-cell DNA/RNA-sequencing analyses and functional experiments, of 19 cases of CLL developing RT. Studying 54 longitudinal samples covering up to 19 years of disease course, we uncovered minute subclones carrying genomic, immunogenetic and transcriptomic features of RT cells already at CLL diagnosis, which were dormant for up to 19 years before transformation. We also identified new driver alterations, discovered a new mutational signature (SBS-RT), recognized an oxidative phosphorylation (OXPHOS)high-B cell receptor (BCR)low-signaling transcriptional axis in RT and showed that OXPHOS inhibition reduces the proliferation of RT cells. These findings demonstrate the early seeding of subclones driving advanced stages of cancer evolution and uncover potential therapeutic targets for RT.
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NADEU PRAT, Ferran, et al. Detection of early seeding of Richter transformation in chronic lymphocytic leukemia. Nature Medicine. 2022. Vol. 28, num. 8, pags. 1662-1671. ISSN 1078-8956. [consulted: 9 of June of 2026]. Available at: https://hdl.handle.net/2445/214988