Repurposing anthelmintic agents to eradicate resistant leukemia

Caterina Mezzatesta, Liridon Abduli, Anna Guinot, Cornelia Eckert, Denis Schewe, Marketa Zaliova, Luciana Vinti, Blerim Marovca, Yi Chien Tsai, Silvia Jenni, Julia Aguade-Gorgorio, Arend von Stackelberg, Martin Schrappe, Franco Locatelli, Martin Stanulla, Gunnar Cario, Jean Pierre Bourquin, Beat C. Bornhauser

Research output: Contribution to journalArticlepeer-review


Despite rapid progress in genomic profiling in acute lymphoblastic leukemia (ALL), identification of actionable targets and prediction of response to drugs remains challenging. To identify specific vulnerabilities in ALL, we performed a drug screen using primary human ALL samples cultured in a model of the bone marrow microenvironment combined with high content image analysis. Among the 2487 FDA-approved compounds tested, anthelmintic agents of the class of macrocyclic lactones exhibited potent anti-leukemia activity, similar to the already known anti-leukemia agents currently used in induction chemotherapy. Ex vivo validation in 55 primary ALL samples of both precursor B cell and T-ALL including refractory relapse cases confirmed strong anti-leukemia activity with IC50 values in the low micromolar range. Anthelmintic agents increased intracellular chloride levels in primary leukemia cells, inducing mitochondrial outer membrane depolarization and cell death. Supporting the notion that simultaneously targeting cell death machineries at different angles may enhance the cell death response, combination of anthelmintic agents with the BCL-2 antagonist navitoclax or with the chemotherapeutic agent dexamethasone showed synergistic activity in primary ALL. These data reveal anti-leukemia activity of anthelmintic agents and support exploiting drug repurposing strategies to identify so far unrecognized anti-cancer agents with potential to eradicate even refractory leukemia.

Original languageEnglish
Article number72
JournalBlood Cancer Journal
Issue number6
Publication statusPublished - Jun 1 2020

ASJC Scopus subject areas

  • Hematology
  • Oncology


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