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CLN7 suppression induces apoptosis via mTOR-regulated and chaperone-mediated autophagy in myeloid leukemia cells

Miaomiao Wu1,2, Hui Li1, Sujun Li1

  • 1Department of Hematology, Centre for Leading Medicine and Advanced Technologies of Institute of Health and Medicine, The First Affiliated Hospital of University of Science and Technology of China, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.

Cell Death & Disease
|May 30, 2026
PubMed

Insights

Targeting the CLN7 lysosomal ion channel shows promise for treating myeloid leukemia. Suppressing CLN7 induces cancer cell death and inhibits tumor growth, offering a new therapeutic strategy for refractory disease.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Refractory myeloid leukemia and relapse remain significant clinical challenges.
  • Lysosomal ion channels are emerging as key regulators of cell death pathways.
  • Identifying novel therapeutic targets is crucial for improving treatment outcomes.

Purpose of the Study:

  • To investigate the role of the lysosomal ion channel CLN7 in myeloid leukemia.
  • To evaluate CLN7 as a potential therapeutic target for myeloid leukemia treatment.

Main Methods:

  • Quantification of CLN7 expression in myeloid leukemia cells.
  • Inhibition of CLN7 using genetic or pharmacological approaches.
  • Assessment of apoptosis, proliferation, and oncogenic protein levels.
  • Analysis of TFEB nuclear translocation, mTOR signaling, lysosomal biogenesis, and autophagy.
  • Evaluation of BCR-ABL degradation and autophagy-mediated apoptosis.
  • Assessment of therapeutic efficacy in combination with chemotherapy.
  • Tumor growth assessment in human xenograft models.

Main Results:

  • CLN7 expression is elevated in myeloid leukemia cells.
  • Suppression of CLN7 induces apoptosis, inhibits proliferation, and reduces oncogenic proteins.
  • CLN7 inhibition promotes TFEB nuclear translocation, enhances lysosomal biogenesis and autophagy.
  • CLN7 suppression upregulates CTSB, accelerating BCR-ABL degradation via chaperone-mediated autophagy.
  • Inhibition of CLN7 triggers autophagy-mediated apoptosis and impairs leukemogenic potential.
  • Combined CLN7 suppression and chemotherapy enhance therapeutic efficacy.
  • CLN7 suppression reduces tumor growth in vivo without affecting normal hematopoietic function.

Conclusions:

  • CLN7 is a critical regulator of leukemic cell survival in myeloid leukemia.
  • Targeting CLN7 represents a promising therapeutic strategy for myeloid leukemia, including refractory cases.
  • CLN7 inhibition offers a selective approach with minimal impact on normal hematopoietic cells.

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