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

Gianpietro Dotti, Enrico Garattini, Gianmaria Borleri, Kensaku Masuhara, Orietta Spinelli, Tiziano Barbui, Alessandro Rambaldi

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)163-172
Number of pages10
JournalBritish Journal of Haematology
Volume105
Issue number1
DOIs
Publication statusPublished - 1999

Keywords

  • Chronic myelogenous leukaemia
  • G-CSF
  • Granulocyte differentiation
  • Leucocyte alkaline phosphatase
  • Tyrosine kinase activity

ASJC Scopus subject areas

  • Hematology

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