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Myelodysplasias

Frequent elevation of Akt kinase phosphorylation in blood marrow and peripheral blood mononuclear cells from high-risk myelodysplastic syndrome patients

Leukemia volume 20, pages 230–238 (2006)Cite this article

Abstract

The serine/threonine kinase Akt, a downstream effector of phosphatidylinositol 3-kinase (PI3K), is known to play an important role in antiapoptotic signaling and has been implicated in the aggressiveness of a number of different human cancers including acute myeloid leukemia (AML). The progression of myelodysplastic syndromes (MDSs) to AML is thought to be associated with abrogation of apoptotic control mechanisms. However, little is known about signal transduction pathways which may be involved in enhanced survival of MDS cells. In this report, we have performed immunocytochemical and flow cytometric analysis to evaluate the levels of activated Akt in bone marrow or peripheral blood mononuclear cells from patients diagnosed with MDS. We observed high levels of Ser473 phosphorylated Akt (p-Akt) staining in 90% of the cases (n=22) diagnosed as high-risk MDS, whereas mononuclear cells from normal bone marrow or low-risk MDS patients showed low or absent Ser473 p-Akt staining. Furthermore, all high-risk MDS patients also demonstrated high expression of the Class I PI3K p110δ catalytic subunit and a decreased expression of PTEN. Taken together, our results suggest that Akt activation might be one of the factors contributing to the decreased apoptosis rate observed in patients with high-risk MDS.

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Acknowledgements

This work was supported by grants from AIRC, Italian MIUR Cofin 2003 and FIRB 2001, ‘Hairshow A.I.L.’, Fondazione del Monte di Bologna e Ravenna.

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Authors and Affiliations

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

    M Nyåkern, M Y Follo, L Cocco & A M Martelli

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

    P L Tazzari

  3. Istituto di Ematologia ed Oncologia Medica Seràgnoli, Università di Bologna, Bologna, Italy

    C Finelli, C Bosi, T Grafone, P P Piccaluga & G Martinelli

  4. Istituto per i Trapianti d'Organo e l'Immunocitologia del C.N.R., Sezione di Bologna c/o I.O.R., Bologna, Italy

    A M Martelli

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  1. M Nyåkern
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Correspondence to A M Martelli.

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Nyåkern, M., Tazzari, P., Finelli, C. et al. Frequent elevation of Akt kinase phosphorylation in blood marrow and peripheral blood mononuclear cells from high-risk myelodysplastic syndrome patients. Leukemia 20, 230–238 (2006). https://doi.org/10.1038/sj.leu.2404057

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