Chidamide inhibits the NOTCH1-MYC signaling axis in T-cell acute lymphoblastic leukemia / 医学前沿
Frontiers of Medicine
;
(4): 442-458, 2022.
Artigo
em Inglês
| WPRIM
| ID: wpr-939877
ABSTRACT
T-cell acute lymphoblastic leukemia (T-ALL) is one of the most dangerous hematological malignancies, with high tumor heterogeneity and poor prognosis. More than 60% of T-ALL patients carry NOTCH1 gene mutations, leading to abnormal expression of downstream target genes and aberrant activation of various signaling pathways. We found that chidamide, an HDAC inhibitor, exerts an antitumor effect on T-ALL cell lines and primary cells including an anti-NOTCH1 activity. In particular, chidamide inhibits the NOTCH1-MYC signaling axis by down-regulating the level of the intracellular form of NOTCH1 (NICD1) as well as MYC, partly through their ubiquitination and degradation by the proteasome pathway. We also report here the preliminary results of our clinical trial supporting that a treatment by chidamide reduces minimal residual disease (MRD) in patients and is well tolerated. Our results highlight the effectiveness and safety of chidamide in the treatment of T-ALL patients, including those with NOTCH1 mutations and open the way to a new therapeutic strategy for these patients.
Texto completo:
DisponíveL
Índice:
WPRIM (Pacífico Ocidental)
Assunto principal:
Benzamidas
/
Linfócitos T
/
Transdução de Sinais
/
Proteínas Proto-Oncogênicas c-myc
/
Linhagem Celular Tumoral
/
Receptor Notch1
/
Leucemia-Linfoma Linfoblástico de Células T Precursoras
/
Aminopiridinas
Limite:
Humanos
Idioma:
Inglês
Revista:
Frontiers of Medicine
Ano de publicação:
2022
Tipo de documento:
Artigo
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