Selective eradication of venetoclax-resistant monocytic acute myeloid leukemia with iron oxide nanozymes.
Biochem Biophys Res Commun
; 719: 150117, 2024 Jul 30.
Article
em En
| MEDLINE
| ID: mdl-38761635
ABSTRACT
The clinical treatment of human acute myeloid leukemia (AML) is rapidly progressing from chemotherapy to targeted therapies led by the BCL-2 inhibitor venetoclax (VEN). Despite its unprecedented success, VEN still encounters clinical resistance. Thus, uncovering the biological vulnerability of VEN-resistant AML disease and identifying effective therapies to treat them are urgently needed. We have previously demonstrated that iron oxide nanozymes (IONE) are capable of overcoming chemoresistance in AML. The current study reports a new activity of IONE in overcoming VEN resistance. Specifically, we revealed an aberrant redox balance with excessive intracellular reactive oxygen species (ROS) in VEN-resistant monocytic AML. Treatment with IONE potently induced ROS-dependent cell death in monocytic AML in both cell lines and primary AML models. In primary AML with developmental heterogeneity containing primitive and monocytic subpopulations, IONE selectively eradicated the VEN-resistant ROS-high monocytic subpopulation, successfully resolving the challenge of developmental heterogeneity faced by VEN. Overall, our study revealed an aberrant redox balance as a therapeutic target for monocytic AML and identified a candidate IONE that could selectively and potently eradicate VEN-resistant monocytic disease.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Sulfonamidas
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Espécies Reativas de Oxigênio
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Resistencia a Medicamentos Antineoplásicos
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Compostos Bicíclicos Heterocíclicos com Pontes
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Antineoplásicos
Limite:
Humans
Idioma:
En
Revista:
Biochem Biophys Res Commun
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
China