Activating mutations remodel the chromatin accessibility landscape to drive distinct regulatory networks in KMT2A-rearranged acute leukemia.

ABSTRACT: Activating FLT3 and RAS mutations commonly occur in leukemia with KMT2A-gene rearrangements (KMT2A-r). However, how these mutations cooperate with the KMT2A-r to remodel the epigenetic landscape is unknown. Using a retroviral acute myeloid leukemia (AML) mouse model driven by KMT2A::MLLT3, we show that FLT3 ^ITD , FLT3 ^N676K , and NRAS ^G12D remodeled the chromatin accessibility landscape and associated transcriptional networks. Although the activating mutations shared a common core of chromatin changes, each mutation exhibits unique profiles with most opened peaks associating with enhancers in intronic or intergenic regions. Specifically, FLT3 ^N676K a

SUBMITTER: Zhang Q 

PROVIDER: S-EPMC11426354 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature