Targeting the lysine-specific demethylase 1 rewires kinase networks and primes leukemia cells for kinase inhibitor treatment
Menée sur des cellules de leucémies myéloïdes aiguës, cette étude met en évidence l'intérêt de cibler la déméthylase LSD1 pour sensibiliser les cellules cancéreuses aux inhibiteurs de MEK
Although some acute myeloid leukemia (AML) cells have mutations that activate the MEK kinase pathway, MEK inhibitors are generally ineffective in treating this cancer. Pedicona et al. integrated phosphoproteomic analysis with drug screening in AML cells from patients and cell lines and correlated kinase network activity with epigenetic markers and kinase inhibitor sensitivity. Inhibiting an enzyme that generates one of those epigenetic markers—lysine-specific demethylase 1 (LSD1)—increased MEK pathway activity while broadly suppressing the activity of other kinases, making cells sensitive to subsequent treatment with a MEK inhibitor. The findings reveal a potential therapeutic strategy for a subset of AML and suggest that activated MEK signaling might be a source of resistance to LSD1 inhibitors now being tested in patients with AML.
Science Signaling 2022