Targeting novel chromatin vulnerabilities in childhood acute myeloid leukemia

Although survival rates in pediatric AML (pAML) increased, a deeper understanding of epigenetic oncogene regulation through long non-coding RNAs opens avenues for novel treatments. In our study, we explore the AML transcriptome landscape by comparing RNA sequencing of pediatric AML patients to healthy individuals. We identified 696 differentially expressed long non-coding RNAs (lncRNAs), implying a potential function in pAML . Utilizing CRISPR/Cas9 inhibition we probed these lncRNAs for function and identified non-coding elements essential in AML development. Validation through knockdown assays followed by quantitative PCR (qPCR) in AML cell lines and patient-derived xenografts (PDX) helped us determine a novel chromatin vulnerability and its relation to oncogene expression. Further analysis with target perturbation followed by a multi-omics approach on transcriptome and chromatin accessibility underscored the critical role of chromatin-mediated oncogene regulation in pediatric AML. Our investigations open new pathways for therapeutic development emphasizing the latent potential of targeting epigenetic mechanisms in combatting this malignant disease.

Publication History

Article published online:
09 May 2025