Selective up-regulation of phospholipase C-β2 during granulocytic differentiation of normal and leukemic hematopoietic progenitors

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.