“Defining Clonal and Metabolic Alterations in the Evolution of RUNX1-FPD”

In RUNX1-FPD, blood stem cell clones can acquire additional mutations, leading to clonal outgrowth and leukemia, but methods to distinguish individual stem cell clones have been limited.

Zon, Liu and Sankran’s study uses cellular barcoding and mitochondrial DNA lineage tracing to identify and track individual stem cell clones in RUNX1-FPD patients, comparing “good” versus “bad” clones. Findings from patient samples will guide experiments in RUNX1-mutant zebrafish, where clonal output and gene function can be tested. The study aims to identify genes and metabolic pathways that drive mutant clones and to evaluate potential drug targets to selectively eliminate bad clones, ultimately providing new therapeutic strategies for RUNX1-FPD.