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1.
Artigo em Chinês | WPRIM | ID: wpr-1017383

RESUMO

Currently, single-cell multi-omics technologies including single-cell DNA sequencing (scDNA-seq) and single-cell RNA sequencing (scRNA-seq) have been used to reveal the heterogeneity of malignant tumor cells, elucidate their pathogenesis, drug resistance and recurrence mechanisms, which provide new strategies for the diagnosis and prognostic assessment of malignant tumors. This article reviews the application of single-cell sequencing technology in the diagnosis and prognostic assessment of acute leukemia based on the progress reported at the 65th American Society of Hematology Annual Meeting.

2.
Frontiers of Medicine ; (4): 442-458, 2022.
Artigo em Inglês | WPRIM | ID: wpr-939877

RESUMO

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.


Assuntos
Humanos , Aminopiridinas , Benzamidas , Linhagem Celular Tumoral , Leucemia-Linfoma Linfoblástico de Células T Precursoras/metabolismo , Proteínas Proto-Oncogênicas c-myc/metabolismo , Receptor Notch1/metabolismo , Transdução de Sinais , Linfócitos T/metabolismo
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