Gene regulatory network analysis predicts cooperating transcription factor regulons required for FLT3-ITD+ AML growth.

ABSTRACT: AML is a heterogenous disease caused by different mutations. We have previously shown that each mutational sub-type develops its specific gene regulatory network (GRN) with transcription factors interacting with multiple gene modules, many of which are transcription factor genes themselves. Here we hypothesized that highly connected nodes within such networks comprise crucial regulators of AML maintenance. We tested this hypothesis using FLT3-ITD mutated AML as a model and conducted an shRNA drop-out screen informed by this analysis. We show that AML-specific GRNs predict identifying crucial regulatory modules required for AML but not normal cellular growth. Furthermore, our work shows that all modules are highly connected and regulate each other. The careful multi-omic analysis of the rol

SUBMITTER: Coleman DJL 

PROVIDER: S-EPMC10370108 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature