Multi-platform profiling characterizes molecular subgroups and resistance networks in chronic lymphocytic leukemia.
Nat Commun
; 12(1): 5395, 2021 09 13.
Article
em En
| MEDLINE
| ID: mdl-34518531
ABSTRACT
Knowledge of the genomic landscape of chronic lymphocytic leukemia (CLL) grows increasingly detailed, providing challenges in contextualizing the accumulated information. To define the underlying networks, we here perform a multi-platform molecular characterization. We identify major subgroups characterized by genomic instability (GI) or activation of epithelial-mesenchymal-transition (EMT)-like programs, which subdivide into non-inflammatory and inflammatory subtypes. GI CLL exhibit disruption of genome integrity, DNA-damage response and are associated with mutagenesis mediated through activation-induced cytidine deaminase or defective mismatch repair. TP53 wild-type and mutated/deleted cases constitute a transcriptionally uniform entity in GI CLL and show similarly poor progression-free survival at relapse. EMT-like CLL exhibit high genomic stability, reduced benefit from the addition of rituximab and EMT-like differentiation is inhibited by induction of DNA damage. This work extends the perspective on CLL biology and risk categories in TP53 wild-type CLL. Furthermore, molecular targets identified within each subgroup provide opportunities for new treatment approaches.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Leucemia Linfocítica Crônica de Células B
/
Regulação Leucêmica da Expressão Gênica
/
Perfilação da Expressão Gênica
/
Instabilidade Genômica
/
Redes Reguladoras de Genes
/
Transição Epitelial-Mesenquimal
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Nat Commun
Assunto da revista:
BIOLOGIA
/
CIENCIA
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Alemanha