High-throughput approaches to uncover synergistic drug combinations in leukemia.
SLAS Discov
; 28(4): 193-201, 2023 06.
Article
em En
| MEDLINE
| ID: mdl-37121274
ABSTRACT
We report a comprehensive drug synergy study in acute myeloid leukemia (AML). In this work, we investigate a panel of cell lines spanning both MLL-rearranged and non-rearranged subtypes. The work comprises a resource for the community, with many synergistic drug combinations that could not have been predicted a priori, and open source code for automation and analyses. We base our definitions of drug synergy on the Chou-Talalay method, which is useful for visualizations of synergy experiments in isobolograms, and median-effects plots, among other representations. Our key findings include drug synergies affecting the chromatin state, specifically in the context of regulation of the modification state of histone H3 lysine-27. We report open source high throughput methodology such that multidimensional drug screening can be accomplished with equipment that is accessible to most laboratories. This study will enable preclinical investigation of new drug combinations in a lethal blood cancer, with data analysis and automation workflows freely available to the community.
Palavras-chave
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Leucemia Mieloide Aguda
/
Proteína de Leucina Linfoide-Mieloide
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
SLAS Discov
Ano de publicação:
2023
Tipo de documento:
Article