Nadeu 2022 Nat Med

From Bioblast
Publications in the MiPMap
Nadeu F, Royo R, Massoni-Badosa R, Playa-Albinyana H, Garcia-Torre B, Duran-Ferrer M, Dawson KJ, Kulis M, Diaz-Navarro A, Villamor N, Melero JL, Chapaprieta V, Dueso-Barroso A, Delgado J, Moia R, Ruiz-Gil S, Marchese D, GirΓ³ A, Verdaguer-Dot N, Romo M, Clot G, Rozman M, Frigola G, Rivas-Delgado A, Baumann T, Alcoceba M, GonzΓ‘lez M, Climent F, Abrisqueta P, CastellvΓ­ J, Bosch F, Aymerich M, Enjuanes A, Ruiz-GaspΓ  S, LΓ³pez-Guillermo A, Jares P, BeΓ  S, Capella-Gutierrez S, GelpΓ­ JL, LΓ³pez-Bigas N, Torrents D, Campbell PJ, Gut I, Rossi D, Gaidano G, Puente XS, Garcia-Roves PM, Colomer D, Heyn H, Maura F, MartΓ­n-Subero JI, Campo E (2022) Detection of early seeding of Richter transformation in chronic lymphocytic leukemia.

Β» Nat Med 28:1662-71. PMID: 35953718 Open Access

Nadeu Ferran, Royo Romina, Massoni-Badosa Ramon, Playa-Albinyana Heribert, Garcia-Torre Beatriz, Duran-Ferrer Marti, Dawson Kevin J, Kulis Marta, Diaz-Navarro Ander, Villamor Neus, Melero Juan L, Chapaprieta Vicente, Dueso-Barroso Ana, Delgado Julio, Moia Riccardo, Ruiz-Gil Sara, Marchese Domenica, Giro Ariadna, Verdaguer-Dot Nuria, Romo Monica, Clot Guillem, Rozman Maria, Frigola Gerard, Rivas-Delgado Alfredo, Baumann Tycho, Alcoceba Miguel, Gonzalez Marcos, Climent Fina, Abrisqueta Pau, Castellvi Josep, Bosch Francesc, Aymerich Marta, Enjuanes Anna, Ruiz-Gaspa Silvia, Lopez-Guillermo Armando, Jares Pedro, Bea Silvia, Capella-Gutierrez Salvador, Gelpi Josep Ll, Lopez-Bigas Nuria, Torrents David, Campbell Peter J, Gut Ivo, Rossi Davide, Gaidano Gianluca, Puente Xose S, Garcia-Roves Pablo M, Colomer Dolors, Heyn Holger, Maura Francesco, Martin-Subero Jose I, Campo Elias (2022) Nat Med

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.

β€’ Bioblast editor: Plangger M β€’ O2k-Network Lab: ES Barcelona Garcia-Roves PM, ES Barcelona IDIBAPS Hospital Clinic

Labels: MiParea: Respiration  Pathology: Cancer 

Organism: Human  Tissue;cell: Blood cells, Lymphocyte  Preparation: Intact cells 

Coupling state: LEAK, ROUTINE, ET  Pathway: ROX  HRR: Oxygraph-2k 


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