Functional characterization of the PI3K/AKT/MTOR signaling pathway for targeted therapy in B-precursor acute lymphoblastic leukemia.

ABSTRACT: B-cell precursor acute lymphoblastic leukemias (B-ALL) are characterized by the activation of signaling pathways, which are involved in survival and proliferation of leukemia cells. Using an unbiased shRNA library screen enriched for targeting signaling pathways, we identified MTOR as the key gene on which human B-ALL E2A-PBX1⁺ RCH-ACV cells are dependent. Using genetic and pharmacologic approaches, we investigated whether B-ALL cells depend on MTOR upstream signaling pathways including PI3K/AKT and the complexes MTORC1 or MTORC2 for proliferation and survival in vitro and in vivo. Notably, the combined inhibition of MTOR and AKT shows a synergistic effect on decreased cell proliferation in B-ALL with different karyotypes. Hence, B-ALL cells were more dependent on MTORC2 rather

SUBMITTER: Gruninger PK 

PROVIDER: S-EPMC9663301 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature