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

Autor: Hidemasa Matsuo, Aina Inagami, Yuri Ito, Nana Ito, Shinju Iyoda, Yutarou Harata, Moe Higashitani, Kota Shoji, Miu Tanaka, Mina Noura, Takashi Mikami, Itaru Kato, Junko Takita, Tatsutoshi Nakahata, Souichi Adachi
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Communications Biology, Vol 7, Iss 1, Pp 1-9 (2024)
Druh dokumentu: article
ISSN: 2399-3642
DOI: 10.1038/s42003-024-05811-8
Popis: 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.
Databáze: Directory of Open Access Journals
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