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Survival of acute myeloid leukemia cells requires PI3 kinase activation

Xu, Qing, Simpson, Serge-Emile, Scialla, Timothy J., Bagg, Adam, Carroll, Martin·2003·Blood
DOI 10.1182/blood-2002-11-3429
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Abstract

The mechanisms that regulate the growth and survival of acute myeloid leukemia (AML) cells are largely unknown. We hypothesized that constitutive activation of phosphatidyl-inositide 3 kinase (PI3 kinase) could regulate survival in primary cells from patients with AML. Here we demonstrate that Akt, a critical substrate of PI3 kinase, is activated in AML blasts. In a short-term culture system, most AML patient samples showed a dose-dependent decrease in survival after incubation with the PI3 kinase inhibitor LY294002. This decrease in survival was partially due to the induction of apoptosis. Furthermore, we have shown that p70 S6 kinase and 4EBP-1, downstream mediators of Akt signaling, also are phosphorylated in AML blasts. Phosphorylation of these proteins is inhibited by the mTOR inhibitor RAD001. Incubation of AML blasts with RAD001 induces only a small decrease in survival of the cells; however, when combined with Ara-C, RAD001 enhances the toxicity of Ara-C. These results demonstrate that constitutive activation of the PI3 kinase pathway is necessary for the survival of AML blasts and that targeting of this pathway with pharmacologic inhibitors may be of clinical benefit in treatment of AML.

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Metadata

Authors
Xu, Q., Simpson, S.-E., Scialla, T. J., Bagg, A., & Carroll, M.
Venue
Blood
Publisher
American Society of Hematology
Published
2003-08-01
Volume
102
Issue
3
Pages
972-980
ISSN
  • 0006-4971
  • 1528-0020
DOI
10.1182/blood-2002-11-3429
Cited by
394
References
2
Language
en

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CoChat. (2026). Citation check: Survival of acute myeloid leukemia cells requires PI3 kinase activation. https://app.cochat.ai/papers/10.1182/blood-2002-11-3429
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Xu, Q., Simpson, S.-E., Scialla, T. J., Bagg, A., & Carroll, M. (2003). Survival of acute myeloid leukemia cells requires PI3 kinase activation. Blood. https://doi.org/10.1182/blood-2002-11-3429