CDK7/12/13 inhibition targets an oscillating LSC network and synergizes with venetoclax in AML

ABSTRACT: The heterogeneous response of acute myeloid leukemia (AML) to current anti-leukemic therapies is only partially explained by mutational heterogeneity. We previously identified GPR56 as surface marker associated with poor outcome across genetic groups, which characterizes two leukemia stem cell (LSC)-enriched compartments with different self-renewal capacities. How these compartments self-renew remained unclear. Here, we show that GPR56+ LSC compartments are promoted in a complex network involving epithelial-to-mesenchymal transition (EMT) regulators besides Rho, Wnt, and Hedgehog (Hh) signaling. Unexpectedly, Wnt pathway inhibition increased the more immature, slowly cycling GPR56+CD34+ fraction and Hh/EMT gene expression, while Wnt activation caused opposite effects. Our data suggest tha

SUBMITTER: Dr. Caroline Pabst 

PROVIDER: S-SCDT-EMM-2021-14990 | biostudies-other |

REPOSITORIES: biostudies-other