Granulocyte Colony-Stimulating Factor Receptor at Various Differentiation Stages of Normal and Leukemic Hematopoietic Cells

Abstract

Granulocyte colony-stimulating factor (G-CSF) is the most important cytokine in granulopoiesis, and induces the proliferation and differentiation of normal bone marrow granulocytic precursors. The physiologic effect of G-CSF is mediated through binding to specific cell surface receptors for G-CSF. Using a newly-devised quantitative flow-cytometric assay, we analyzed the expression of G-CSF receptors on normal and leukemic hematopoietic cells. In normal donors, G-CSF receptors are widely expressed from CD34-positive immature bone marrow cells to mature peripheral granulocytes. The highest expression of G-CSF receptors is observed in peripheral granulocytes. In the bone marrow, the level of G-CSF receptors expression increases in the following order; CD34+CD33- cells < CD34+CD33+ cells < CD34-CD33+ cells, indicating that G-CSF receptors are expressed on myeloid cells from a very early stage of differentiation and that the level of expression increases with the progress of cell maturation. G-CSF receptors are also detected on blast cells of patients with acute myeloid leukemia (AML) and acute lymphoid leukemia (ALL). The number of cell surface receptors varies from patient to patient, and no clear correlation is observed between the expression of receptors and the leukemia subtype or the cell surface markers. In this respect, the clinical use of G-CSF should be carefully controlled in ALL as well as AML patients.