TY - JOUR
T1 - Selective up-regulation of phospholipase C-β2 during granulocytic differentiation of normal and leukemic hematopoietic progenitors
AU - Bertagnolo, Valeria
AU - Marchisio, Marco
AU - Pierpaoli, Sabina
AU - Colamussi, Maria Luisa
AU - Brugnoli, Federica
AU - Visani, Giuseppe
AU - Zauli, Giorgio
AU - Capitani, Silvano
PY - 2002/6/1
Y1 - 2002/6/1
N2 - In this study, we have investigated the expression of phospholipase C-β2 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 transretinoic acid (ATRA) by differentiating in a neutrophil-like manner. We found that PLC-β2, virtually absent in untreated NB4 cells, was strongly upregulated 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-β2 expression and the responsiveness of APL blasts to the differentiative activity of ATRA. An increase of PLC-β2 expression also characterized the cytokine-induced granulocytic differentiation of CD34+ normal hematopoietic progenitors. Taken together, these data show that PLC-β2 represents a sensitive and reliable marker of neutrophil maturation of normal and malignant myeloid progenitors. Moreover, PLC-β2 levels can predict the in vivo responsiveness to ATRA of APL patients.
AB - In this study, we have investigated the expression of phospholipase C-β2 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 transretinoic acid (ATRA) by differentiating in a neutrophil-like manner. We found that PLC-β2, virtually absent in untreated NB4 cells, was strongly upregulated 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-β2 expression and the responsiveness of APL blasts to the differentiative activity of ATRA. An increase of PLC-β2 expression also characterized the cytokine-induced granulocytic differentiation of CD34+ normal hematopoietic progenitors. Taken together, these data show that PLC-β2 represents a sensitive and reliable marker of neutrophil maturation of normal and malignant myeloid progenitors. Moreover, PLC-β2 levels can predict the in vivo responsiveness to ATRA of APL patients.
KW - Cellular differentiation
KW - Hematopoiesis
KW - Lipid mediators
KW - Neutrophils
KW - Signal transduction
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M3 - Article
C2 - 12050180
AN - SCOPUS:0036622946
VL - 71
SP - 957
EP - 965
JO - Journal of Leukocyte Biology
JF - Journal of Leukocyte Biology
SN - 0741-5400
IS - 6
ER -