Related Experiment Video
Updated: Apr 12, 2026

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants
Published on: June 6, 2025
Co-activation of AMPK and mTORC1 Induces Cytotoxicity in Acute Myeloid Leukemia
Pierre Sujobert1, Laury Poulain1, Etienne Paubelle2
1INSERM U1016, Institut Cochin, 75014 Paris, France; CNRS UMR8104, 75014 Paris, France; Université Paris Descartes, Faculté de Médecine Sorbonne Paris Cité, 75005 Paris, France; Equipe Labellisée Ligue Nationale Contre le Cancer (LNCC), 75013 Paris, France.
Abstract:
AMPK is a master regulator of cellular metabolism that exerts either oncogenic or tumor suppressor activity depending on context. Here, we report that the specific AMPK agonist GSK621 selectively kills acute myeloid leukemia (AML) cells but spares normal hematopoietic progenitors. This differential sensitivity results from a unique synthetic lethal interaction involving concurrent activation of AMPK and mTORC1. Strikingly, the lethality of GSK621 in primary AML cells and AML cell lines is abrogated by chemical or genetic ablation of mTORC1 signaling. The same synthetic lethality between AMPK and mTORC1 activation is established in CD34-positive hematopoietic progenitors by constitutive activation of AKT or enhanced in AML cells by deletion of TSC2. Finally, cytotoxicity in AML cells from GSK621 involves the eIF2α/ATF4 signaling pathway that specifically results from mTORC1 activation. AMPK activation may represent a therapeutic opportunity in mTORC1-overactivated cancers.
Related Concept Videos
mTOR Signaling and Cancer Progression
The mTOR pathway or the...
mTOR Signaling and Cancer Progression
PI3K/mTOR/AKT Signaling Pathway
MAPK Signaling Cascades
The Intrinsic Apoptotic Pathway
Interactions Between Signaling Pathways
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...

