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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 <jats:italic>AKT1<\/jats:italic> knockdown, which induced massive cell death in pAKT<jats:sup>high<\/jats:sup> 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 version of AKT (myrAKT) or knockdown of <jats:italic>PTEN<\/jats:italic> repressed the growth of BL cell lines. This was associated with increased AKT phosphorylation, NF-\u03baB activation, and downregulation of DZ genes including the proto-oncogene <jats:italic>MYB<\/jats:italic> and the DZ marker CXCR4. In contrast to GCB-DLBCL, PTEN overexpression was tolerated by BL cell lines. We conclude that the molecular mechanisms instrumental to guarantee the survival of normal DZ B cells, including the tight regulation of the PTEN-PI3K-AKT axis, also operate in the survival\/proliferation of BL.<\/jats:p>","DOI":"10.1038\/s41375-019-0628-0","type":"journal-article","created":{"date-parts":[[2019,12,16]],"date-time":"2019-12-16T14:51:14Z","timestamp":1576507874000},"page":"857-871","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Physiological levels of the PTEN-PI3K-AKT axis activity are required for maintenance of Burkitt lymphoma"],"prefix":"10.1038","volume":"34","author":[{"given":"Franziska","family":"Gehringer","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie Ellen","family":"Weissinger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"M\u00f6ller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Wirth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3724-7253","authenticated-orcid":false,"given":"Alexey","family":"Ushmorov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,11,12]]},"reference":[{"key":"628_CR1","doi-asserted-by":"publisher","first-page":"pii: a014282","DOI":"10.1101\/cshperspect.a014282","volume":"4","author":"R Schmitz","year":"2014","unstructured":"Schmitz R, Ceribelli M, Pittaluga S, Wright G, Staudt LM. 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