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Updated: Dec 17, 2025

Modeling Chemotherapy Resistant Leukemia In Vitro
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Repurposing anthelmintic agents to eradicate resistant leukemia.

Caterina Mezzatesta1, Liridon Abduli1, Anna Guinot1

  • 1Department of Oncology and Children's Research Center, Children's Hospital Zurich, Lengghalde 5, Balgrist Campus AG, 8008, Zurich, Switzerland.

Blood Cancer Journal
|June 28, 2020
PubMed
Summary

Anthelmintic drugs show potent anti-leukemia activity against acute lymphoblastic leukemia (ALL) by increasing chloride levels and inducing cell death. Combining these agents with other therapies may enhance effectiveness against refractory leukemia.

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Area of Science:

  • Hematology
  • Oncology
  • Pharmacology

Background:

  • Genomic profiling in acute lymphoblastic leukemia (ALL) has advanced, yet identifying drug targets and predicting treatment response remains difficult.
  • Discovering novel therapeutic strategies is crucial for overcoming drug resistance and improving outcomes in ALL.

Purpose of the Study:

  • To identify novel anti-leukemia vulnerabilities in acute lymphoblastic leukemia (ALL) through drug repurposing.
  • To evaluate the efficacy of FDA-approved compounds, particularly anthelmintic agents, against primary ALL cells.

Main Methods:

  • A drug screen of 2487 FDA-approved compounds was conducted on primary human ALL samples within a bone marrow microenvironment model.
  • High-content image analysis was used to assess drug efficacy.
  • Ex vivo validation was performed on 55 primary ALL samples, including refractory and relapsed cases.

Main Results:

  • Macrocyclic lactone anthelmintic agents demonstrated potent anti-leukemia activity, comparable to current induction chemotherapy agents.
  • Anthelmintic agents increased intracellular chloride levels, leading to mitochondrial depolarization and cell death in leukemia cells.
  • Synergistic anti-leukemia effects were observed when combining anthelmintic agents with navitoclax or dexamethasone.

Conclusions:

  • Anthelmintic agents possess significant anti-leukemia activity and represent a promising avenue for drug repurposing in ALL treatment.
  • Targeting cell death pathways with anthelmintic agents, especially in combination therapies, holds potential for eradicating refractory leukemia.