By transplanting in competition multiple pre-leukemic clones in a cohort of primary recipients, we observed emergence of dominant clones during the development of AML. By sampling winner clones at different time points, we could observe the gradual acquisition a of cell-intrinsic growth advantage that was preserved in secondary transplantation, whereas control loser clones grew at a significantly lower rate. Functional characterization of the winner clones demonstrated a higher engraftment rate in vivo, whereas the self-renewal potential and growth rate in vitro was similar among winner and loser clones. By comparing the gene expression profile of leukemic stem cells isolated from various clones, we observed that the most aggressive clones share a common signature characterized by activation of multiple metabolic pathways, such as steroid biosynthesis and response to oxidative stress. SOURCE: Jiantao Shi (jshi@hsph.harvard.edu) - Michor lab dana farber cancer institute

Pluto Bioinformatics

GSE121354: In Vivo Profiling of Leukemic Stem Cell Fitness