2. Academic Validation
  3. Decursin induces FLT3-ITD acute myeloid leukemia cell apoptosis by increasing the expression of the ubiquitin-conjugase UBE2L6

Decursin induces FLT3-ITD acute myeloid leukemia cell apoptosis by increasing the expression of the ubiquitin-conjugase UBE2L6

  • Cell Commun Signal. 2025 Apr 2;23(1):162. doi: 10.1186/s12964-025-02157-4.
Tianxin Zhang # 1 2,  Yuchen Li # 1,  Wenhao Liao 3,  Yu Mou 4,  Xue Zhan 4,  Qiongying Hu # 5,  Ziyi Zhao # 6 7,  Daqian Xiong # 8 9
Affiliations

Affiliations

  • 1 Department of Laboratory Medicine, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, 610072, China.
  • 2 College of Medical Technology, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China.
  • 3 Department of Nephrology, the Key Laboratory for the Prevention and Treatment of Chronic Kidney Disease of Chongqing, Chongqing Clinical Research Center of Kidney and Urology Diseases, Xinqiao Hospital, Army Medical University, Third Military Medical University), Chongqing, 400037, China.
  • 4 Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, 610072, China.
  • 5 Department of Laboratory Medicine, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, 610072, China. qiongyinghu@163.com.
  • 6 Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, 610072, China. zhaoziyi@cdutcm.edu.cn.
  • 7 TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, 610072, China. zhaoziyi@cdutcm.edu.cn.
  • 8 Department of Laboratory Medicine, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, 610072, China. 705006714@qq.com.
  • 9 College of Medical Technology, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China. 705006714@qq.com.
  • # Contributed equally.
PMID: 40176110 DOI: 10.1186/s12964-025-02157-4
Abstract

Mutation in the internal tandem duplication sequence of the FLT3 gene (FLT3-ITD) is linked to a poor clinical prognosis in acute myeloid leukemia (AML) patients. FLT3 inhibitors have demonstrated efficacy in improving the prognosis of AML patients with FLT3-ITD. However, the efficacy of FLT3 inhibitors is short-lived, and is often limited by secondary drug resistance when used alone. Recent investigations have provided an innovative approach for treating FLT3-ITD AML by targeting FLT3 protein degradation. Our study revealed that decursin selectively impaired the viability of FLT3-ITD-positive AML cells. Subsequent analysis revealed that decursin preferentially induced cell cycle arrest and Apoptosis in FLT3-ITD-positive AML cells through proteasome-mediated FLT3-ITD degradation. Further research revealed that decursin significantly increased the expression of UBE2L6, an e2-conjugating enzyme that degrades FLT3-ITD. Downregulation of UBE2L6 by small hairpin RNA (shRNA) reduced decursin-induced FLT3-ITD-linked Apoptosis and degradation. The anti-FLT3-ITD AML effect of decursin was also validated in cell lines and patient-derived mouse models. Moreover, decursin synergistically enhanced venetoclax-induced Apoptosis.

Keywords

AML; Decursin; Degradation; FLT3-ITD; UBE2L6.

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