Oncogenic dependency on SWI/SNF chromatin remodeling factors in T-cell acute lymphoblastic leukemia.
Leukemia
; 38(9): 1906-1917, 2024 Sep.
Article
em En
| MEDLINE
| ID: mdl-38969731
ABSTRACT
T-cell acute lymphoblastic leukemia (T-ALL) is a hematological malignancy arising from immature thymocytes. Unlike well-known oncogenic transcription factors, such as NOTCH1 and MYC, the involvement of chromatin remodeling factors in T-ALL pathogenesis is poorly understood. Here, we provide compelling evidence on how SWI/SNF chromatin remodeling complex contributes to human T-ALL pathogenesis. Integrative analysis of transcriptomic and ATAC-Seq datasets revealed high expression of SMARCA4, one of the subunits of the SWI/SNF complex, in T-ALL patient samples and cell lines compared to normal T cells. Loss of SMARCA protein function resulted in apoptosis induction and growth inhibition in multiple T-ALL cell lines. ATAC-Seq analysis revealed a massive reduction in chromatin accessibility across the genome after the loss of SMARCA protein function. RUNX1 interacts with SMARCA4 protein and co-occupies the same genomic regions. Importantly, the NOTCH1-MYC pathway was primarily affected when SMARCA protein function was impaired, implicating SWI/SNF as a novel therapeutic target.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Fatores de Transcrição
/
Proteínas Nucleares
/
DNA Helicases
/
Montagem e Desmontagem da Cromatina
/
Leucemia-Linfoma Linfoblástico de Células T Precursoras
Limite:
Humans
Idioma:
En
Revista:
Leukemia
Assunto da revista:
HEMATOLOGIA
/
NEOPLASIAS
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Singapura