Chidamide inhibits the NOTCH1-MYC signaling axis in T-cell acute lymphoblastic leukemia / 医学前沿
Frontiers of Medicine
; (4): 442-458, 2022.
Article
in En
| WPRIM
| ID: wpr-939877
Responsible library:
WPRO
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.
Key words
Full text:
1
Index:
WPRIM
Main subject:
Benzamides
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T-Lymphocytes
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Signal Transduction
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Proto-Oncogene Proteins c-myc
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Cell Line, Tumor
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Receptor, Notch1
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Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
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Aminopyridines
Limits:
Humans
Language:
En
Journal:
Frontiers of Medicine
Year:
2022
Type:
Article