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Phosphoinositide 3-kinase/Akt signaling pathway and its therapeutical implications for human acute myeloid leukemia

Leukemia volume 20, pages 911–928 (2006)Cite this article

Abstract

The phosphoinositide 3-kinase (PI3K)/Akt signaling pathway is crucial to many aspects of cell growth, survival and apoptosis, and its constitutive activation has been implicated in the both the pathogenesis and the progression of a wide variety of neoplasias. Hence, this pathway is an attractive target for the development of novel anticancer strategies. Recent studies showed that PI3K/Akt signaling is frequently activated in acute myeloid leukemia (AML) patient blasts and strongly contributes to proliferation, survival and drug resistance of these cells. Upregulation of the PI3K/Akt network in AML may be due to several reasons, including FLT3, Ras or c-Kit mutations. Small molecules designed to selectively target key components of this signal transduction cascade induce apoptosis and/or markedly increase conventional drug sensitivity of AML blasts in vitro. Thus, inhibitory molecules are currently being developed for clinical use either as single agents or in combination with conventional therapies. However, the PI3K/Akt pathway is important for many physiological cellular functions and, in particular, for insulin signaling, so that its blockade in vivo might cause severe systemic side effects. In this review, we summarize the existing knowledge about PI3K/Akt signaling in AML cells and we examine the rationale for targeting this fundamental signal transduction network by means of selective pharmacological inhibitors.

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Acknowledgements

This work was supported by grants from: Italian MIUR FIRB 2001 and COFIN 2005, Associazione Italiana Ricerca sul Cancro (AIRC Regional Grants), CARISBO Foundation.

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Authors and Affiliations

  1. Dipartimento di Scienze Anatomiche Umane e Fisiopatologia dell’Apparato Locomotore, Cell Signalling Laboratory, Sezione di Anatomia Umana, Università di Bologna, Bologna, Italy

    A M Martelli, M Nyåkern, C Evangelisti & L Cocco

  2. ITOI-CNR, c/o IOR, Bologna, Italy

    A M Martelli

  3. Dipartimento di Scienze Biomediche e Biotecnologie, Sezione di Citologia e Istologia, Università di Brescia, Brescia, Italy

    G Tabellini

  4. Dipartimento di Morfologia Umana Normale, Università di Trieste, Trieste, Italy

    R Bortul

  5. Servizio di Immunoematologia e Trasfusionale, Policlinico S.Orsola-Malpighi, Bologna, Italy

    P L Tazzari

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  1. A M Martelli
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  2. M Nyåkern
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  3. G Tabellini
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  4. R Bortul
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  5. P L Tazzari
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  6. C Evangelisti
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  7. L Cocco
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Correspondence to A M Martelli.

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Martelli, A., Nyåkern, M., Tabellini, G. et al. Phosphoinositide 3-kinase/Akt signaling pathway and its therapeutical implications for human acute myeloid leukemia. Leukemia 20, 911–928 (2006). https://doi.org/10.1038/sj.leu.2404245

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  • DOI: https://doi.org/10.1038/sj.leu.2404245

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