Co-operative epigenetic remodelling by Setd2 deficiency and Kras mutation drives juvenile myelomonocytic leukaemia development and MEK inhibitor sensitivity.

ABSTRACT: Juvenile myelomonocytic leukaemia (JMML) primarily stems from the Rat Sarcoma (RAS)/Extracellular Signal-Regulated Kinase (ERK) pathway mutations, and currently, there are no effective regimens against JMML, yet various studies have highlighted the importance of deciphering secondary genetic and/or epigenetic alterations in pursuit of treatments. Setd2-mediated-H3K36me3 participates in myriad biological functions and primarily serves as a tumour suppressor gene in carcinogenesis. However, little is known about the synergism between Setd2 deficiency and Kras mutation during JMML onset and progression. Herein, we reveal that Kras-mutant JMML possesses a lower H3K36 trimethylation mark, and Setd2 ablation in the KrasG12D/+-mediated JMML model shortens the disease latency. Phenotypically, Setd

SUBMITTER: Munyurangabo G 

PROVIDER: S-EPMC12512064 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature