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

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.