Parbendazole as a promising drug for inducing differentiation of acute myeloid leukemia cells with various subtypes.
Hidemasa MatsuoAina InagamiYuri ItoNana ItoShinju IyodaYutarou HarataMoe HigashitaniKota ShojiMiu TanakaMina NouraTakashi MikamiItaru KatoJunko TakitaTatsutoshi NakahataSouichi AdachiPublished in: Communications biology (2024)
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.
Keyphrases
- acute myeloid leukemia
- allogeneic hematopoietic stem cell transplantation
- cell cycle arrest
- induced apoptosis
- gene expression
- mouse model
- endoplasmic reticulum stress
- cell death
- dna methylation
- endothelial cells
- high glucose
- dendritic cells
- molecular docking
- drug induced
- pi k akt
- stem cells
- diabetic rats
- metabolic syndrome
- immune response
- transcription factor
- newly diagnosed
- stress induced