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Mechanistic Insights into the Epigenetic Regulation and Therapeutic Targeting of RET Receptor Tyrosine Kinase in KMT2A-Rearranged Pediatric Acute Myeloid Leukemia

ABSTRACT: Pediatric acute myeloid leukemia (pAML) driven by KMT2A gene rearrangements (KMT2A-r; 11q23 translocations) is a high-risk leukemia with limited treatment options and a poor prognosis. Previously, we reported (PMID: 38226414) that the RET receptor tyrosine kinase is epigenetically upregulated in major KMT2A-r subgroups. In this study, we utilized a synthetic drug, 8p, which serves as a dual inhibitor of RET and cyclin-dependent kinase 8 (CDK8). We conducted RNA sequencing analysis on 8p-treated KMT2A-MLLT3 fusion-positive MOLM-13 cells to profile genome-wide gene expression changes. This study enhances our understanding of the major pathways affected by the dual inhibition of RET and CDK8 in KMT2A-r AML.

ORGANISM(S): Homo sapiens

PROVIDER: GSE291525 | GEO | 2026/04/01

REPOSITORIES: GEO

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