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Blood, 15 January 2006, Vol. 107, No. 2, pp. 508-513.
Prepublished online as a Blood First Edition Paper on September 15, 2005; DOI 10.1182/blood-2005-07-2676.
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Submitted July 7, 2005
Accepted September 1, 2005
PKC controls the protection against TRAIL in erythroid progenitors
Prisco Mirandola, Giuliana Gobbi, Cristina Ponti, Ivonne Sponzilli, Lucio Cocco, and Marco Vitale*
Department of Anatomy, Pharmacology & Forensic Medicine, Human Anatomy Section, University of Parma, Parma, Italy
Department of Normal Human Morphology, University of Trieste, Trieste, Italy
Dept. of Anatomical Sciences, Cellular Signaling Laboratory, University of Bologna, Bologna, Italy
Department of Anatomy, Pharmacology & Forensic Medicine, Human Anatomy Section, University of Parma, Parma, Italy; ITOI-CNR, Bologna Unit, c/o Research Institute "Codivilla-Putti", Bologna, Italy
* Corresponding author; email: marco.vitale{at}unipr.it.
Apoptosis plays a central role in the regulation of the size of the hematopoietic stem cell pool as well as in the processes of cell differentiation along the various hematopoietic lineages. TRAIL is a member of the TNF family of cytokines with a known apoptogenic role against a variety of malignant cells and an emerging role in the modulation of normal hematopoiesis. Here we worked on the hypotesis that PKC could act as a switch of the cellular response to TRAIL during erythropoiesis.
We demonstrate that EPO-induced erythroid CD34 cells are insensitive to the apoptogenic effect of TRAIL at day 0 due to the lack of specific receptors expression. From day 3 onward, erythroid cells express surface death receptors and become sensitive to TRAIL up to day 7/8 when, notwithstanding death receptor expression, the EPO-driven up-regulation of PKC intracellular levels renders differentiating erythoid cells resistant to TRAIL likely via Bcl-2 up-regulation. Our conclusion is that in human CD34 cells EPO promotes a series of events that, being finely regulated in their kinetics, restrict the sensitivity of these cells to TRAIL to a specific period of time, that therefore represents the "TRAIL window" for the negative regulation of erythroid cell number.

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