2. Academic Validation
  3. Parbendazole as a promising drug for inducing differentiation of acute myeloid leukemia cells with various subtypes

Parbendazole as a promising drug for inducing differentiation of acute myeloid leukemia cells with various subtypes

  • Commun Biol. 2024 Jan 24;7(1):123. doi: 10.1038/s42003-024-05811-8.
Hidemasa Matsuo 1,  Aina Inagami 2,  Yuri Ito 2,  Nana Ito 2,  Shinju Iyoda 2,  Yutarou Harata 2,  Moe Higashitani 2,  Kota Shoji 2,  Miu Tanaka 2,  Mina Noura 3,  Takashi Mikami 4,  Itaru Kato 4,  Junko Takita 4,  Tatsutoshi Nakahata 5,  Souichi Adachi 2
Affiliations

Affiliations

  • 1 Human Health Sciences, Graduate School of Medicine, Kyoto University, Kyoto, Japan. [email protected].
  • 2 Human Health Sciences, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
  • 3 Department of Integrated Health Sciences, Division of Cellular and Genetic Sciences, Nagoya University Graduate School of Medicine, Nagoya, Japan.
  • 4 Department of Pediatrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
  • 5 Department of Fundamental Cell Technology, Center for iPS Cell Research and Application, Kyoto University, Kyoto, Japan.
PMID: 38267545 DOI: 10.1038/s42003-024-05811-8
Abstract

Acute myeloid leukemia (AML) is a malignancy characterized by differentiation arrest of hematopoietic precursor cells. Differentiation therapy is effective for patients with acute promyelocytic leukemia; however, only a few effective differentiation therapies have been established for patients with other AML subtypes. In this study, seven benzimidazole anthelmintics were examined to determine the effects of differentiation on AML cells. The expression of monocyte markers (CD11b and CD14) was elevated after treatment with most benzimidazole anthelmintics. Among these drugs, parbendazole (PBZ) induced AML cell differentiation at low concentration. PBZ induced the monocyte marker expression, KLF4/DPYSL2A gene expression, and Apoptosis for 21 AML cell lines with various subtypes and a primary AML sample. Finally, an in vivo analysis using an AML patient-derived xenograft mouse model showed a significant decrease in the chimerism level and prolonged survival in PBZ-treated mice. These findings could lead to a more effective differentiation therapy for AML.

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