Induction of Neutrophil Alkaline Phosphatase Gene Expression by Granulocyte Colony-stimulating Factor in Chronic Myelogenous Leukemia

The mechanism underlying defective neutrophil alkaline phosphatase (NAP) activity in chronic myelogenous leukemia (CML) was examined using Northern blotting analysis and NAP staining. Fourteen patients with Ph1-positive CML in the chronic phase were included in this study. Polymorphonuclear cells (PMN), containing more than 80% of stab and segmented neutrophils, were collected from peripheral blood (PB) by methylcellulose sedimentation after density gradient centrifugation. Neutrophil alkaline phosphatase mRNA (NAPmRNA) expression was very weak in all patients. When incubated with granulocyte colony-stimulating factor (G-CSF) for 24 h, the PMN of all patients expressed a detectable level of NAPmRNA. NAP score, which semiquantitatively reflects the activity of gene products, was also elevated after incubation with G-CSF in 12 patients. However, a higher dose of G-CSF was required for the maximum response than was the case for normal bone marrow PMN, which also manifested increases of NAPmRNA and its products on stimulation by G-CSF. The present study suggests that the PMN of CML express NAPmRNA and produce its products in response to G-CSF, but that they are less sensitive to G-CSF than normal bone marrow PMN.