Detection of early seeding of Richter transformation in chronic lymphocytic leukemia.
Journal
Nature medicine
ISSN: 1546-170X
Titre abrégé: Nat Med
Pays: United States
ID NLM: 9502015
Informations de publication
Date de publication:
08 2022
08 2022
Historique:
received:
10
11
2021
accepted:
01
07
2022
pubmed:
12
8
2022
medline:
23
8
2022
entrez:
11
8
2022
Statut:
ppublish
Résumé
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)
Identifiants
pubmed: 35953718
doi: 10.1038/s41591-022-01927-8
pii: 10.1038/s41591-022-01927-8
pmc: PMC9388377
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1662-1671Subventions
Organisme : Cancer Research UK
Pays : United Kingdom
Informations de copyright
© 2022. The Author(s).
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