title: S-phase cells of the lymphoplasmocytic compartment in hyperdiploid multiple myeloma are diploid cells.
abstract: In vivo S-phase cell labeling with iododexoyuridine (IdUrd) was performed in six multiple myeloma (MM) patients. Myeloma cells from four patients were hyperploid. In three out of four patients, DNA/IdUrd flow cytometry revealed that most of the labeled cells, which had divided during the period, elapsed between flash labeling and sampling, had returned to the diploid G0/G1 compartment and not to the hyperdiploid peak. To eliminate contaminating cells belonging to the normal hematopoiesis, plasmocytic and lymphocytic cells were fractionated and analyzed separately. Cell enrichment was performed with use of murine monoclonal antibodies (MoAbs) against plasmocytic and lymphocytic cell markers and subsequent magnetic activated cell sorting with immunobeads, i.e., polysterene magnetic particles coated with sheep anti-mouse IgG. The purified plasmocytic cells were mainly hyperdiploid and largely unlabeled. The lymphocytic cells appeared to belong chiefly to the diploid cell population. The IdUrd-labeled cells were predominantly lymphocytic cells, returning after mitosis to the diploid G0/G1 peak. Although this pattern of S-phase cells in hyperdiploid MM, belonging to the diploid cell compartment, was observed in three out of four hyperploid cases and although the number of observations is small, S-phase cells may demonstrate an aspect of tumor cell kinetics in hyperploid MM, which has been debated for many years and which indicates the existence of a non-plasmocytic stem cell compartment that feeds the plasmocytoma. The behavior of the labeled cells as observed in a few cases of MM provides another, hitherto undescribed, argument that, at least in some MM patients, a part of the proliferating tumor cells may be diploid lymphocytic (precursor) cells. These findings should be considered when targeting and monitoring treatment of MM and also in purging procedures of bone marrow in patients to be treated by ablative cytotoxic therapy and autologous bone marrow transplantation.
authors.affiliation: Department of Medicine, Medical Spectrum Twente, Enschede, The Netherlands.
authors.forename: V
authors.initials: V
authors.lastname: Haraldsdóttir
authors.forename: C
authors.initials: C
authors.lastname: Haanen
authors.forename: E
authors.initials: E
authors.lastname: Kalsbeek-Batenburg
authors.forename: F
authors.initials: F
authors.lastname: Olthuis
mesh_terms: D000368:Aged; D001853:Bone Marrow / Q000473:pathology*; D002453:Cell Cycle; D004273:DNA, Neoplasm / Q000032:analysis*; D004171:Diploidy; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D016193:G1 Phase; D006412:Hematopoietic Stem Cells / Q000473:pathology; D006801:Humans; D007065:Idoxuridine; D008214:Lymphocytes / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000235:genetics / Q000473:pathology*; D009367:Neoplasm Staging; D010950:Plasma Cells / Q000473:pathology; D016192:Resting Phase, Cell Cycle; D016196:S Phase
chemical_list: D004273:DNA, Neoplasm; D007065:Idoxuridine