title: The functional phenotype of the primitive plasma cell in patients with multiple myeloma correlates with the clinical state.
abstract: 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 defined but little is known about the functional differences and clinical significance of these subpopulations. Three colour flow cytometry and permeabilisation was used to determine the expression of functionally important antigens in plasma cell subpopulations. These antigens included the labelling index (LI, bromodeoxyuridine), number of nucleoside transporter 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 progressive disease there was an increase in the absolute number but not the percentage of CD45++ plasma cells. There was a significant difference in the mean LI of the CD38++, CD45++ population in progressive disease 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 correlation 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 plasma cell population. In 96% (n = 28) of samples from patients in progressive disease there was at least one abnormality in the functional phenotype of the primitive plasma cells. This is in contrast with 44% of samples 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.
authors.affiliation: Institute of Haematology, Royal Prince Alfred Hospital, Sydney, Australia.
authors.forename: B
authors.initials: B
authors.lastname: Pope
authors.forename: R D
authors.initials: RD
authors.lastname: Brown
authors.forename: J
authors.initials: J
authors.lastname: Gibson
authors.forename: A
authors.initials: A
authors.lastname: Petersen
authors.forename: J
authors.initials: J
authors.lastname: Wiley
authors.forename: D E
authors.initials: DE
authors.lastname: Joshua
mesh_terms: D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000032:analysis; D015703:Antigens, CD; D018941:Antigens, CD19 / Q000032:analysis; D000943:Antigens, Differentiation / Q000032:analysis; D002352:Carrier Proteins / Q000032:analysis; D005434:Flow Cytometry; D006801:Humans; D008562:Membrane Glycoproteins; D008565:Membrane Proteins / Q000032:analysis; D009101:Multiple Myeloma / Q000473:pathology*; D009244:NAD+ Nucleosidase / Q000032:analysis; D033703:Nucleoside Transport Proteins; D010641:Phenotype; D010950:Plasma Cells / Q000737:chemistry*; D016271:Proto-Oncogene Proteins c-myc / Q000032:analysis
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D015703:Antigens, CD; D018941:Antigens, CD19; D000943:Antigens, Differentiation; D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D033703:Nucleoside Transport Proteins; D016271:Proto-Oncogene Proteins c-myc; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; D009244:NAD+ Nucleosidase; D051997:ADP-ribosyl Cyclase 1