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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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HEMATOPOIESIS
Brief report

Potential role of APRIL as autocrine growth factor for megakaryocytopoiesis

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

From the Laboratory of Hematology and Oncology, Istituto Superiore di Sanità, Rome Italy; Institut de Génétique Moléculaire de Montpellier, Montpellier, France; Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA; and Mediterranean Institute of Oncology, Catania, Italy.

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 healthy donors, but it is massively up-regulated 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 physiologic platelet production.


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