Leucocyte alkaline phosphatase identifies terminally differentiated normalneutrophils and its lack in chronic myelogenous leukaemia is not dependenton p210 tyrosine kinase activity

Leucocyte alkaline phosphatase (LAP) is a marker of post-mitotic granulocyt es and its activity is reduced or absent in chronic myelogenous leukaemia ( CML) granulocytes as a consequence of LAP messenger RNA (mRNA) deficiency. We provide evidence that along the granulocytic maturation in normal marrow , the acquisition of LAP surface expression, identified by the monoclonal a ntibody 1B12.1, was restricted to CD11b(bright)/CD16(bright) positive cells . Moreover, in normal granulocytes, exposure to granulocyte colony-stimulat ing factor (G-CSF) in vitro and in viva increased the cell surface expressi on of LAP. Although G-CSF was able to induce the LAP surface expression in Chit granulocytes, the inhibition of p210 tyrosine kinase activity by genis tein or CGP75148B failed to restore LAP mRNA expression and LAP protein syn thesis, In conclusion, the acquisition of LAP protein on the cell surface o f granulocytes follows CD16 antigen expression and can be considered as the last marker of terminally differentiated neutrophils. G-CSF is a potent re gulator of the LAP mRNA expression and protein synthesis in normal and CML- derived neutrophils. The lack of direct activity of p210 tyrosine kinase on LAP mRNA expression in CML neutrophils supports the notion that the LAP de fect in this disease could be related to a precocious and uncontrolled rele ase of white blood cells from the bone marrow into the blood stream.