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

ABSTRACT: Acute myeloid leukemia (AML) is a heterogeneous disease caused by different mutations. Previously, we showed that each mutational subtype develops its specific gene regulatory network (GRN) with transcription factors interacting within multiple gene modules, many of which are transcription factor genes themselves. Here, we hypothesize that highly connected nodes within such networks comprise crucial regulators of AML maintenance. We test this hypothesis using FLT3-ITD-mutated AML as a model and conduct an shRNA drop-out screen informed by this analysis. We show that AML-specific GRNs predict crucial regulatory modules required for AML growth. Furthermore, our work shows that all modules are highly connected and regulate each other. The careful multi-omic analysis of the role of one (RUNX1)

SUBMITTER: Coleman DJL 

PROVIDER: S-EPMC10874628 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature