Potential role of APRIL as autocrine growth factor for megakaryocytopoiesis.
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.
Bonci
Désirée
D
Laboratory of Hematology and Oncology, Istituto Superiore di Sanità, Rome, Italy.
Hahne
Michael
M
Felli
Nadia
N
Peschle
Cesare
C
De Maria
Ruggero
R
D019898:Autocrine Communication / Q000502:physiology; D001792:Blood Platelets / Q000166:cytology / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D005312:Fetal Blood / Q000166:cytology; D006133:Growth Substances / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008533:Megakaryocytes / Q000166:cytology* / Q000502:physiology*; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism*
C490341:ANP32B protein, human; D006133:Growth Substances; D009687:Nuclear Proteins