Multiple Myeloma: Expression of Nucleoside Transporters on Malignant Plasma Cells and Their Relationship to Cellular Proliferation

Abstract

The expression of nucleoside transporters is a limiting factor in the pharmacology of the nucleoside analogue, cytosine arabinoside (AraC) and is associated with cellular proliferation. We investigated the expression of nucleoside transporters on plasma cells from the bone marrow of 51 patients with multiple myeloma by 2-colour immunofluorescence flow cytometry, utilising 5-(SAENTA-x8)-fluorescein, a fluorescent ligand for the nucleoside transporter and anti-CD38 conjugated to phycoerythrin, as CD38 expression has unique characteristics on plasma cells. Mean nucleoside transporter expression on bone marrow plasma cells from patients with myeloma (1777 ↣ 2181 transporters/plasma cell) was not significantly different from expression on plasma cells from normal bone marrow (997 ↣ 1096 transporters/plasma cell). However, analysis of disease subgroups revealed a significant trend towards increased transporter expression in patients with progressive disease compared to those with stable disease (X² = 4.0, p < 0.05). Nucleoside transporter expression correlated significantly with the plasma cell labelling index (LI) (r = 0.45, p < 0.01) and serum thymidine kinase levels (r = 0.66, p < 0.01), both markers of cellular proliferation but not with c-myc oncoprotein expression. These findings suggest that flow cytometric measurement of nucleoside transporter expression on plasma cells provides a rapid and convenient measurement of disease activity or quiescence in myeloma.