title: Selective up-regulation of phospholipase C-beta2 during granulocytic differentiation of normal and leukemic hematopoietic progenitors.
abstract: In this study, we have investigated the expression of phospholipase C-beta2 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-beta2, 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-beta2 expression and the responsiveness of APL blasts to the differentiative activity of ATRA. An increase of PLC-beta2 expression also characterized the cytokine-induced granulocytic differentiation of CD34+ normal hematopoietic progenitors. Taken together, these data show that PLC-beta2 represents a sensitive and reliable marker of neutrophil maturation of normal and malignant myeloid progenitors. Moreover, PLC-beta2 levels can predict the in vivo responsiveness to ATRA of APL patients.
authors.affiliation: Signal Transduction Unit/Laboratory of Cell Biology, Section of Human Anatomy, Department of Morphology and Embryology, University of Ferrara, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Bertagnolo
authors.forename: Marco
authors.initials: M
authors.lastname: Marchisio
authors.forename: Sabina
authors.initials: S
authors.lastname: Pierpaoli
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Colamussi
authors.forename: Federica
authors.initials: F
authors.lastname: Brugnoli
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Visani
authors.forename: Giorgio
authors.initials: G
authors.lastname: Zauli
authors.forename: Silvano
authors.initials: S
authors.lastname: Capitani
mesh_terms: D000208:Acute Disease; D015703:Antigens, CD / Q000032:analysis; D018952:Antigens, CD34 / Q000032:analysis; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004963:Estrenes / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D006098:Granulocytes / Q000166:cytology / Q000201:enzymology / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000473:pathology; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology; D007527:Isoenzymes / Q000235:genetics*; D007951:Leukemia, Myeloid; D015473:Leukemia, Promyelocytic, Acute; D054799:Phospholipase C beta; D020033:Protein Isoforms / Q000235:genetics; D011760:Pyrrolidinones / Q000494:pharmacology; D014212:Tretinoin / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D010738:Type C Phospholipases / Q000235:genetics*
chemical_list: D015703:Antigens, CD; D018952:Antigens, CD34; D004791:Enzyme Inhibitors; D004963:Estrenes; D007377:Interleukin-3; D007527:Isoenzymes; D020033:Protein Isoforms; D011760:Pyrrolidinones; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; D016179:Granulocyte Colony-Stimulating Factor; D014212:Tretinoin; D010738:Type C Phospholipases; C518036:PLCB2 protein, human; D054799:Phospholipase C beta