Chidamide inhibits the NOTCH1-MYC signaling axis in T-cell acute lymphoblastic leukemia

  • Xi, Mengping
  • Guo, Shanshan
  • Bayin, Caicike
  • Peng, Lijun
  • Chuffart, Florent
  • Bourova-Flin, Ekaterina
  • Rousseaux, Sophie
  • Khochbin, Saadi
  • Mi, Jian-Qing
  • Wang, Jin
Publication date
January 2021
Publisher
Springer Science and Business Media LLC

Abstract

International audienceT-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 TALL 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 TALL 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 preli...

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