Targeting the fetal transcriptional landscape of pediatric AML

Despite significant progress in the treatment of pediatric acute myeloid leukemia (AML), infant leukemia remains a clinical challenge. The presence of oncogenic events specific to infants with AML indicates a fetal origin. We hypothesized that the fetal transcriptomic landscape harbors specific vulnerabilities in infant AML. Utilizing CRISPR/Cas knock-out screens aimed at genes overexpressed in fetal hematopoietic stem and progenitor cells, we examined various cell lines and murine models. Our bioinformatic analysis revealed regulatory genes involved in pivotal cellular processes such as the cell cycle, cell proliferation and apoptosis, uncovering novel therapeutic targets across infant and pediatric AML subtypes. Selected candidates were subsequently validated in cell lines by knock-out assays. One candidate stood out in this analysis and is an interesting link between metabolism and epigenetic regulation. Ongoing research will further elucidate the contribution of this fetal gene to infant leukemia pathogenesis. This study underscores the potential of targeting fetal-origin vulnerabilities in infant AML, paving the way for innovative treatment strategies.

Publication History

Article published online:
09 May 2025