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* Signal Transduction Unit/Laboratory of Cell Biology, Section of Human Anatomy, Department of Morphology and Embryology, and
# MIUR ICSI (Interdisciplinary Center for the Study of Inflammation), University of Ferrara, Italy;
Department of Biomorphology, University "G.D’Annunzio", Chieti, Italy;
Department of Pathology, Uniformed Services University of the Health Sciences, Bethesda, Maryland;
L.A. Seragnoli Institute of Haematology, University of Bologna, Italy; and
|| Department of Normal Human Morphology, University of Trieste, Italy
Correspondence: Silvano Capitani, Signal Transduction Unit/Laboratory of Cell Biology, Section of Human Anatomy, Department of Morphology and Embryology, University of Ferrara, Via Fossato di Mortara, 66, 44100 Ferrara, Italy. E-mail: cps{at}dns.unife.it
In this study, we have investigated the expression of phospholipase C-ß2 during the course of granulocytic differentiation of normal and malignant progenitors. As a model system, we used the NB4 cell line, a reliable in vitro model for the study of acute promyelocytic leukemia (APL), a variety of acute myeloid leukemia (AML) that responds to pharmacological doses of all trans-retinoic acid (ATRA) by differentiating in a neutrophil-like manner. We found that PLC-ß2, virtually absent in untreated NB4 cells, was strongly up-regulated after ATRA-induced granulocytic differentiation. Remarkably, using primary blasts purified from bone marrow of patients affected by APL successfully induced to remission by treatment with ATRA, we showed a striking correlation between the amount of PLC-ß2 expression and the responsiveness of APL blasts to the differentiative activity of ATRA. An increase of PLC-ß2 expression also characterized the cytokine-induced granulocytic differentiation of CD34+ normal hematopoietic progenitors. Taken together, these data show that PLC-ß2 represents a sensitive and reliable marker of neutrophil maturation of normal and malignant myeloid progenitors. Moreover, PLC-ß2 levels can predict the in vivo responsiveness to ATRA of APL patients.
Key Words: neutrophils • cellular differentiation • hematopoiesis • signal transduction • lipid mediators
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