RUNX1-ETO oncoprotein levels determine the balance between endothelial reprogramming and pre-leukemic growth in a human ES cell model of AML
Abstract
In t(8;21) acute myeloid leukemia (AML), the RUNX1 DNA binding domain is fused to RUNX1T1 (ETO) producing the RUNX1-ETO fusion protein. We previously showed that t(8;21) leukemic stem cells aberrantly activate endothelial signaling pathways to initiate blast cell proliferation. Here, we employed a human embryonic stem cell (ESC) line carrying an inducible RUNX1-ETO transgene to determine whether endothelial signaling pathway activation depends on disease progression or is directly induced by RUNX1-ETO. Single-cell analyses demonstrate that RUNX1-ETO reprograms ESC-derived myeloid progenitors towards endothelial cells. We show (1) that endothelial reprogramming is RUNX1-ETO concentration-dependent and irreversible, (2) at similar RUNX1-ETO and RUNX1 expression levels, a sub-population of blood progenitors can escape reprogramming, and (3) keeps proliferating when co-cultured with endothelial cells. Our experiments highlight the role of cellular interactions in the maintenance of pre-leukemic cells and provide important insights into the earliest stages of genomic reprogramming by oncogenic transcription factors.
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BibTeX
@article{terolli2026runx1eto,
title = {{RUNX1-ETO oncoprotein levels determine the balance between endothelial reprogramming and pre-leukemic growth in a human ES cell model of AML}},
author = {Katerina Terolli and Floyd Hassenrueck and Alexander Maytum and Peter Keane and Lea Flippe and Sophie G. Kellaway and Merel van der Meulen and Olaf T. Heidenreich and Edouard G. Stanley and Elizabeth S. Ng and Andrew G. Elefanty and Constanze Bonifer},
journal = {Cell Reports},
year = {2026},
month = oct,
doi = {10.1016/j.celrep.2026.118157},
url = {https://linkinghub.elsevier.com/retrieve/pii/S2211124726012362},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - RUNX1-ETO oncoprotein levels determine the balance between endothelial reprogramming and pre-leukemic growth in a human ES cell model of AML
AU - Katerina Terolli
AU - Floyd Hassenrueck
AU - Alexander Maytum
AU - Peter Keane
AU - Lea Flippe
AU - Sophie G. Kellaway
AU - Merel van der Meulen
AU - Olaf T. Heidenreich
AU - Edouard G. Stanley
AU - Elizabeth S. Ng
AU - Andrew G. Elefanty
AU - Constanze Bonifer
PY - 2026
DA - 2026/10/01
JO - Cell Reports
DO - 10.1016/j.celrep.2026.118157
UR - https://linkinghub.elsevier.com/retrieve/pii/S2211124726012362
AB - In t(8;21) acute myeloid leukemia (AML), the RUNX1 DNA binding domain is fused to RUNX1T1 (ETO) producing the RUNX1-ETO fusion protein. We previously showed that t(8;21) leukemic stem cells aberrantly activate endothelial signaling pathways to initiate blast cell proliferation. Here, we employed a human embryonic stem cell (ESC) line carrying an inducible RUNX1-ETO transgene to determine whether endothelial signaling pathway activation depends on disease progression or is directly induced by RUNX1-ETO. Single-cell analyses demonstrate that RUNX1-ETO reprograms ESC-derived myeloid progenitors towards endothelial cells. We show (1) that endothelial reprogramming is RUNX1-ETO concentration-dependent and irreversible, (2) at similar RUNX1-ETO and RUNX1 expression levels, a sub-population of blood progenitors can escape reprogramming, and (3) keeps proliferating when co-cultured with endothelial cells. Our experiments highlight the role of cellular interactions in the maintenance of pre-leukemic cells and provide important insights into the earliest stages of genomic reprogramming by oncogenic transcription factors.
SN - 2211-1247
ER -