Physiological levels of the PTEN-PI3K-AKT axis activity are required for maintenance of Burkitt lymphoma.

ABSTRACT: In addition to oncogenic MYC translocations, Burkitt lymphoma (BL) depends on the germinal centre (GC) dark zone (DZ) B cell survival and proliferation programme, which is characterized by relatively low PI3K-AKT activity. Paradoxically, PI3K-AKT activation facilitates MYC-driven lymphomagenesis in mice, and it has been proposed that PI3K-AKT activation is essential for BL. Here we show that the PI3K-AKT activity in primary BLs and BL cell lines does not exceed that of human non-neoplastic tonsillar GC DZ B cells. BLs were not sensitive to AKT1 knockdown, which induced massive cell death in pAKT^high DLBCL cell lines. Likewise, BL cell lines show low sensitivity to pan-AKT inhibitors. Moreover, hyper-activation of the PI3K-AKT pathway by overexpression of a constitutively active

SUBMITTER: Gehringer F 

PROVIDER: S-EPMC7214272 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature