THE FUNCTIONAL PHENOTYPE OF THE PRIMITIVE PLASMA-CELL IN PATIENTS WITH MULTIPLE-MYELOMA CORRELATES WITH THE CLINICAL STATE

The malignant plasma cells from patients with multiple myeloma display considerable phenotypic heterogeneity. All plasma cells express high intensity CD38 (CD38(++)), cytoplasmic immunoglobulin and either kappa or lambda light chains. Subpopulations of mature (CD45(-)), immature (CD45(+)) and primitive (CD45(++), CD19(+)) plasma cells can be define d but little is known about the functional differences and clinical si gnificance of these subpopulations. Three colour flow cytometry and pe rmeabilisation was used to determine the expression of functionally im portant antigens in plasma cell subpopulations. These antigens include d the labelling index (LI, bromodeoxyuridine), number of nucleoside tr ansporter per cell, p-glycoprotein (JSB-1), and oncoprotein expression (c-myc, c-fos, c-neu, bcl-2, p-ras, p53m, p-53w, and Rb). In progress ive disease there was an increase in the absolute number but not the p ercentage of CD45(++) plasma cells. There was a significant difference in the mean LI of the CD38(++), CD45(++) population in progressive di sease compared with stable disease (9.2% vs 2.2%; z = 19.9, p < 0.001) . The LI of CD45(++) cells ranged up to 45%, and provided a better cor relation with disease status than the LI of the total cell population. Any increase in nucleoside transporters or p-glycoprotein expression was almost entirely attributable to an increase in the primitive plasm a cell population. In 96% (n = 28) of samples from patients in progres sive disease there was at least one abnormality in the functional phen otype of the primitive plasma cells. This is in contrast with 44% of s amples from patients in stable disease (n = 58). These studies suggest that the functional phenotype of the primitive plasma cell determines the clinical phenotype of patients with myeloma.