RUNX1-ETO oncoprotein levels determine the balance between endothelial reprogramming and pre-leukemic growth in a human ES cell model of AML.

RUNX1-ETO levels determine endothelial reprogramming and pre-leukemic growth in human ESC-derived myeloid progenitors, with reprogramming being concentration-dependent and irreversible.

• Why it matters: Understanding how oncogenic transcription factors like RUNX1-ETO influence early leukemia development can reveal targets for intervention and clarify disease progression mechanisms.
• What they did: Using an inducible RUNX1-ETO transgene in human embryonic stem cells, the study employed single-cell analyses to examine how varying RUNX1-ETO levels affect endothelial reprogramming and cell proliferation, identifying sub-populations that escape reprogramming.
• The result: Findings show that endothelial reprogramming is driven by RUNX1-ETO concentration and remains irreversible, with some blood progenitors continuing to proliferate alongside endothelial cells, shedding light on early leukemia cell maintenance.