Albendazole induces the terminal differentiation of acute myeloid leukaemia cells to monocytes by stimulating the Krüppel-like factor 4-dihydropyrimidinase-like 2A (KLF4-DPYSL2A) axis

Mina Noura; Ken Morita; Hiroki Kiyose; Yukiko Okuno; Hidemasa Matsuo; Asami Koyama; Yoko Nishinaka-Arai; Yasuhiko Kamikubo; Souichi Adachi

doi:10.1111/bjh.17557

Albendazole induces the terminal differentiation of acute myeloid leukaemia cells to monocytes by stimulating the Krüppel-like factor 4-dihydropyrimidinase-like 2A (KLF4-DPYSL2A) axis

Br J Haematol. 2021 Aug;194(3):598-603. doi: 10.1111/bjh.17557. Epub 2021 Jul 5.

Authors

Affiliations

¹ Department of Human Health Sciences, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
² Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
³ Medical Research Support Center, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
⁴ Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan.
⁵ Department of Pediatrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan.

PMID: 34227104
DOI: 10.1111/bjh.17557

Abstract

Differentiation therapy is a less toxic but still a very effective treatment for a subset of acute myeloid leukaemia (AML) cases. With the goal to identify novel compounds that can effectively and safely induce the terminal differentiation of non-acute promyelocytic leukaemia (APL) AML cells, we performed a chemical screening and identified albendazole (ABZ), a widely used anti-helminthic drug, as a promising lead compound that can differentiate non-APL AML cells by stimulating the Krüppel-like factor 4-dihydropyrimidinase-like 2A (KLF4-DPYSL2A) differentiation axis to the monocytes. Our in vitro and in vivo findings demonstrate that ABZ is an attractive candidate drug as a novel differentiation chemotherapy for patients with non-APL AML.

Keywords: AML; differentiation; leukaemia.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Albendazole / pharmacology*
Albendazole / therapeutic use
Animals
Anthelmintics / pharmacology*
Anthelmintics / therapeutic use
Antineoplastic Agents / pharmacology*
Antineoplastic Agents / therapeutic use
Cell Differentiation / drug effects
Cell Line, Tumor
Humans
Intercellular Signaling Peptides and Proteins / metabolism*
Kruppel-Like Factor 4 / metabolism*
Leukemia, Myeloid, Acute / drug therapy*
Leukemia, Myeloid, Acute / metabolism
Leukemia, Myeloid, Acute / pathology
Mice
Monocytes / drug effects
Nerve Tissue Proteins / metabolism*
Signal Transduction / drug effects

Substances

Anthelmintics
Antineoplastic Agents
Intercellular Signaling Peptides and Proteins
Kruppel-Like Factor 4
Nerve Tissue Proteins
collapsin response mediator protein-2
Albendazole