2. Academic Validation
  3. KIF11 promotes AML progression, and its inhibition by SB-743921 suppresses disease advancement through mitotic G2/M phase arrest

KIF11 promotes AML progression, and its inhibition by SB-743921 suppresses disease advancement through mitotic G2/M phase arrest

  • Cell Signal. 2025 Nov:135:111980. doi: 10.1016/j.cellsig.2025.111980.
Linbo Cai 1,  Jianwei Wang 2,  Yang Yang 2,  Jia Cheng 1,  Yan Wei 3,  Xin Su 4,  Qing Zhu 5,  Juanjuan Yu 1,  Yanling Chen 1,  Ying Yang 1,  Fenli Zhang 1,  Yifang Ding 6,  Mengmeng Gu 4,  Zong Zhai 4,  Hongli Yin 2,  Zhiheng Li 2,  Yanfang Tao 4,  Di Wu 2,  Gen Li 2,  Zimu Zhang 2,  Xiaolu Li 2,  Jian Pan 7,  Peifang Xiao 8
Affiliations

Affiliations

  • 1 Children's Hospital of Soochow University, Suzhou 215003, China.
  • 2 Institute of Pediatric Research, Children's Hospital of Soochow University, Suzhou 215003, China.
  • 3 Affiliated Children's Hospital of Jiangnan University, Wuxi 214000, China.
  • 4 Department of Hematology, Children's Hospital of Soochow University, Suzhou 215003, China.
  • 5 Department of Pediatrics, The Third people's Hospital of Kunshan, Suzhou 215003, China.
  • 6 Department of Pediatrics, The Affiliated Zhangjiagang Hospital of Soochow University, Suzhou 215003, China.
  • 7 Institute of Pediatric Research, Children's Hospital of Soochow University, Suzhou 215003, China. Electronic address: panjian2008@163.com.
  • 8 Department of Hematology, Children's Hospital of Soochow University, Suzhou 215003, China. Electronic address: xpfdr@163.com.
PMID: 40659169 DOI: 10.1016/j.cellsig.2025.111980
Abstract

Acute myeloid leukaemia (AML) is a heterogeneous haematological malignancy. Despite advances in therapy, its prognosis remains poor with limited improvement in survival. KIF11 (Eg5), a Kinesin motor protein essential for spindle dynamics during Mitosis, interacts with microtubules. Inhibition of KIF11 disrupts spindle poles, impairs chromosome segregation, and induces mitotic arrest and Apoptosis, making it a potential therapeutic target. SB-743921, a selective KIF11 inhibitor, has shown potent anti-tumour activity in various cancers. It effectively inhibits AML cell proliferation, induces cell cycle arrest, and suppresses tumour progression. In vitro, it exhibits potent cytotoxic activity against various AML cell lines, and KIF11 knockdown further confirms its pivotal role in AML. RNA Sequencing reveals that SB-743921 downregulates key pathways (e.g. MYC, E2F and G2M). In vivo, SB-743921 delays tumour growth and prolongs survival in AML mice with minimal toxicity, thus supporting its clinical potential. These findings support further investigation on clinical applications and clinical strategies for addressing of this challenging disease.

Keywords

Acute Myeloid Leukaemia (AML); Cell cycle; KIF11; Motor protein; SB-743921.

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