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 Blood, 15 November 2004, Vol. 104, No. 10, pp. 3169-3172.
Prepublished online as a Blood First Edition Paper on April 22, 2004; DOI 10.1182/blood-2003-11-3861.

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Submitted November 12, 2003
Accepted April 8, 2004

Potential role of APRIL as autocrine growth factor for megakaryocytopoiesis

Desiree Bonci, Michael Hahne, Nadia Felli, Cesare Peschle, and Ruggero De Maria*

Ematologia, Oncologia e Medicina Molecolare, Istituto Superiore di Sanita, Roma, Italy, Italy
Institut de Genetique Moleculaire de Montpellier, UMR 5535/CNRS, Montpellier, France, France
Ematologia, Oncologia e Medicina Molecolare, Istituto Superiore di Sanita, Roma, Italy, Italy; Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA
Ematologia, Oncologia e Medicina Molecolare, Istituto Superiore di Sanita, Roma, Italy, Italy; Department of Experimental Oncology, Istituto Oncologico del Mediterraneo, Catania, Italy, Italy

* Corresponding author; email: rdemaria{at}tin.it.

A Proliferation Inducing Ligand (APRIL) is a new tumor necrosis factor family member implicated in tumor cell proliferation. We investigated the role of APRIL in megakaryocytopoiesis, a developmental hematopoietic process responsible for progenitor cell differentiation to megakaryoblasts and megakaryocytes, leading to platelet formation. APRIL is not expressed in CD34+ progenitor cells from normal donors, but it is massively upregulated during the proliferative phase of megakaryocytic cell differentiation. Exogenous APRIL expression in primary cells increases megakaryocytic cell growth, suggesting that APRIL acts as a proliferative factor in megakaryocytopoiesis. More importantly, neutralization of endogenous APRIL was able to dramatically reduce megakaryocyte expansion and platelet production. Thus, our data provide evidence that APRIL acts as a growth factor for terminal megakaryocytopoiesis and may promote physiological platelet production.


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D. Bonci, M. Musumeci, V. Coppola, A. Addario, C. Conticello, M. Hahne, M. Gulisano, F. Grignani, and R. De Maria
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