Thank you! Your submission has been received!
Oops! Something went wrong while submitting the form.
X
Announcing the new Tapestri Solution for Solid Tumor Oncology Research. Learn More
X
publication

Detection of early seeding of Richter transformation in chronic lymphocytic leukemia


Ferran Nadeu et al.
Nature Medicine (2022)
Abstract

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.



Authors

Ferran Nadeu, Romina Royo, Ramon Massoni-Badosa, Heribert Playa-Albinyana, Beatriz Garcia-Torre, Martí Duran-Ferrer, Kevin J. Dawson, Marta Kulis, Ander Diaz-Navarro, Neus Villamor, Juan L. Melero, Vicente Chapaprieta, Ana Dueso-Barroso, Julio Delgado, Riccardo Moia, Sara Ruiz-Gil, Domenica Marchese, Ariadna Giró, Núria Verdaguer-Dot, Mónica Romo, Guillem Clot, Maria Rozman, Gerard Frigola, Alfredo Rivas-Delgado, Tycho Baumann, Miguel Alcoceba, Marcos González, Fina Climent, Pau Abrisqueta, Josep Castellví, Francesc Bosch, Marta Aymerich, Anna Enjuanes, Sílvia Ruiz-Gaspà, Armando López-Guillermo, Pedro Jares, Sílvia Beà, Salvador Capella-Gutierrez, Josep Ll. Gelpí, Núria López-Bigas, David Torrents, Peter J. Campbell, Ivo Gut, Davide Rossi, Gianluca Gaidano, Xose S. Puente, Pablo M. Garcia-Roves, Dolors Colomer, Holger Heyn, Francesco Maura, José I. Martín-Subero, Elías Campo



VIEW

publication
Single cell genotypic and phenotypic analysis of measurable residual disease in acute myeloid leukemia
Troy T. Robinson
publication
The genomic landscape of pediatric acute lymphoblastic leukemia
Samuel W. Brady
Nature Genetics
publication
Modeling clonal evolution and oncogenic dependency in vivo in the context of hematopoietic transformation
Bowman RL
BioRxiv (2022)
publication
Distinct patterns of clonal evolution drive myelodysplastic syndrome progression to secondary acute myeloid leukemia
Guess T
Blood Cancer Discovery (2022)
REQUEST QUOTE