Exogenous expression of human granulocyte colonystimulating factor receptor in a B-lineage acute lymphoblastic leukemia cell line: A possible model for mixed lineage leukemia

Abstract

We report evidence that the granulocyte colony-stimulating factor (G-CSF) receptor is present and may be functioning on blast cells from some patients with myeloid surface antigen positive (My +) acute lymphoblastic leukemia (ALL). In the present study, a human G-CSF receptor expression plasmid was transfected into a newly established B-lineage ALL cell line ‘Tanoue’ and its subclone ‘ST’ by lipofection to investigate whether expression of the G-CSF receptor and G-CSF stimulation would induce myeloid characteristics on myeloid surface antigen negative (My −) ALL cells. The G-CSF receptor became detectable on the transfected cells (GR-Tanoue and GR-ST), with dissociation constant values of 50–130 pmol/l, and maximal binding sites ( B max of 77–6100 sites/cell on receptor binding assays. Short term culture with recombinant human G-CSF induced myeloid differentiation (a two to three-fold increase in CD33 and CD15 expression), and a moderate 3H-thymidine uptake (stimulation index, 1.75) only in the GR-ST clone no. 15 which expressed a high number of G-CSF receptors ( B max, 6100 sites/cell). Our data show that (a) exogenous expression of the G-CSF receptor and G-CSF stimulation can induce myeloid characteristics on ALL cells; and (b) in the G-CSF receptorexpressing cells, there is a correlation between the number of G-CSF receptors and cell responsiveness to G-CSF in either proliferation or differentiation.