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Cited by 277

The DOI matches its Crossref record; 82 of the 82 references it cites were found in a registry or an index.

Constitutive activation of Akt contributes to the pathogenesis and survival of mantle cell lymphoma

Open access
Rudelius, Martina, Pittaluga, Stefania, Nishizuka, Satoshi, Pham, Trinh H.-T., Fend, Falko, Jaffe, Elaine S., Quintanilla-Martinez, Leticia, Raffeld, Mark·2006·Blood

Abstract

To determine whether the PI3K/Akt signaling pathway is involved in the pathogenesis of mantle cell lymphoma (MCL), we investigated the phosphorylation status of Akt and multiple downstream targets in primary MCL cases and cell lines. Akt was phosphorylated in 12 of 12 aggressive blastoid MCL variants and in 4 of 4 MCL cell lines. In contrast, phosphorylated Akt was present in only 5 of 16 typical MCL, 3 at comparable levels to the blastoid cases, and 2 at low levels. The presence of p-Akt was accompanied by the phosphorylation of p27kip1, FRKHL-1, MDM2, Bad, mTOR, and p70S6K. Inhibition of the PI3K/Akt pathway in the MCL cell lines abrogated or reduced the phosphorylation of Akt, p27kip1, FRKHL-1, MDM2, Bad, mTOR, GSK-3β, IκB, and led to cell-cycle arrest and apoptosis. Six MCL cases (5 with activated Akt and 1 with inactive Akt) and 3 of 4 cell lines showed loss of PTEN expression. PIK3CA mutations were not detected. We conclude that constitutive activation of the PI3K/Akt pathway contributes to the pathogenesis of MCL and preferentially occurs in blastoid variants. One possible mechanism of activation is loss of PTEN expression. These data suggest that PI3K/Akt inhibitors may be effective in the treatment of Akt-activated MCL.

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Metadata

Authors
Rudelius, M., Pittaluga, S., Nishizuka, S., Pham, T. H.-T., Fend, F., Jaffe, E. S., Quintanilla-Martinez, L., & Raffeld, M.
Venue
Blood
Published
2006-09-01
Volume
108
Issue
5
Pages
1668-1676
ISSN
  • 0006-4971 (ISSN-L)
  • 1528-0020
OpenAlex
W2011102246
Cited by
277
References
82
FWCI
12.29
Type
journal article
Language
en
Open access
bronze

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CoChat. (2026). Citation check: Constitutive activation of Akt contributes to the pathogenesis and survival of mantle cell lymphoma. https://app.cochat.ai/papers/10.1182/blood-2006-04-015586
The paper
Rudelius, M., Pittaluga, S., Nishizuka, S., Pham, T. H.-T., Fend, F., Jaffe, E. S., Quintanilla-Martinez, L., & Raffeld, M. (2006). Constitutive activation of Akt contributes to the pathogenesis and survival of mantle cell lymphoma. Blood. https://doi.org/10.1182/blood-2006-04-015586

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

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