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ACSL1 promotes imatinib-induced chronic myeloid leukemia cell senescence by regulating SIRT1/p53/p21 pathway

Wen Liu1, Xiaoying Zhu1, Ling Tang1

  • 1Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.

Scientific Reports
|October 26, 2022
PubMed

Insights

Long-chain acyl-CoA synthetase 1 (ACSL1) promotes chronic myeloid leukemia (CML) cell senescence and tumor growth. Targeting the ACSL1/SIRT1/p53 pathway may eradicate CML leukemia stem cells (LSCs).

Area of Science:

  • Oncology
  • Molecular Biology
  • Cellular Senescence

Background:

  • Tyrosine kinase inhibitors (TKIs) improve chronic myeloid leukemia (CML) prognosis but face resistance and residual leukemia stem cells (LSCs).
  • Cellular senescence is crucial for CML cure, and lipid metabolism influences senescence.
  • Long-chain acyl-CoA synthetase 1 (ACSL1) is upregulated in senescent CML cells.

Purpose of the Study:

  • Investigate the role of ACSL1 in CML cell senescence and its interaction with imatinib.
  • Elucidate the molecular mechanisms underlying ACSL1-induced senescence in CML.
  • Identify ACSL1 as a potential therapeutic target for CML eradication.

Main Methods:

  • Overexpression and knockdown of ACSL1 in K562 cells.
  • Cell cycle analysis and proliferation assays.
  • In vivo tumorigenicity studies in K562 xenograft models.
  • Western blot analysis of the SIRT1/p53/p21 pathway.

Main Results:

  • ACSL1 overexpression induces senescence, inhibits cell growth, and enhances imatinib's effect in K562 cells.
  • ACSL1 overexpression reduces tumor growth in vivo.
  • ACSL1 knockdown reverses imatinib-induced senescence.
  • ACSL1 induces senescence via the SIRT1/p53/p21 axis.

Conclusions:

  • ACSL1 promotes imatinib-induced senescence and tumor growth in CML by regulating the SIRT1/p53/p21 pathway.
  • The ACSL1/SIRT1/p53 axis is a novel mechanism for CML cell senescence.
  • Targeting ACSL1 offers a potential strategy for eradicating CML LSCs.

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