Leucocyte alkaline phosphatase identifies terminally differentiated normal neutrophils and its lack in chronic myelogenous leukaemia is not dependent on p210 tyrosine kinase activity

Abstract

Summary. Leucocyte alkaline phosphatase (LAP) is a marker of post-mitotic granulocytes 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 antibody 1B12.1, was restricted to CD11b bright /CD16 bright positive cells. Moreover, in normal granulocytes, exposure to granulocyte colony-stimulating factor (G-CSF) in vitro and in vivo increased the cell surface expression of LAP. Although G-CSF was able to induce the LAP surface expression in CML granulocytes, the inhibition of p210 tyrosine kinase activity by genistein or CGP75148B failed to restore LAP mRNA expression and LAP protein synthesis. In conclusion, the acquisition of LAP protein on the cell surface of granulocytes follows CD16 antigen expression and can be considered as the last marker of terminally differentiated neutrophils. G-CSF is a potent regulator 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 defect in this disease could be related to a precocious and uncontrolled release of white blood cells from the bone marrow into the blood stream.

Role of cardiolipins, mitochondria, and autophagy in the differentiation process activated by all-trans retinoic acid in acute promyelocytic leukemia

“…NB4 cell exposure to the highest concentration of ethanolamine is also associated with an attenuation in the ATRA-dependent increase of CD11c. The suppressive action of ethanolamine on CD11b and CD11c is specific, as the compound does not affect CD33, a myeloid marker which is not modulated by ATRA in APL cells [ 13 , 26 ]. Further support to the idea that ethanolamine inhibits the granulocytic differentiation process ignited by ATRA in NB4 cells comes from the measurement of two other markers, PU.1 and IRF1, which are transcription-factors involved in the control of myeloid maturation [ 27 , 28 ].…”

Definition, Epidemiology, Pathophysiology, and Essential Criteria for Diagnosis of Pediatric Chronic Myeloid Leukemia

“…The leukocyte (neutrophil) alkaline phosphatase (LAP) level as a marker of terminally differentiated neutrophilic granulocytes is decreased in CML [95,96]. Antigens normally found on neutrophils (CD15, HLA-DR) may be expressed weakly.…”