Hyperdiploid Multiple Myeloma Research Articles

Hyperdiploid myeloma cell as an indicator of poor prognosis and drug refractoriness.

Although almost 40% of patients with multiple myeloma respond to initial chemotherapy, myeloma with no response to initial chemotherapy remains a serious problem. To understand the characteristics of drug-refractoriness of myeloma, fresh tumor cells from 13 untreated myeloma patients were fixed and stained with anti-human immunoglobulins and propidium iodide for subsequent flow cytometric analysis of DNA content. More than 10% of myeloma cells were hyperdiploid in eight cases (hyperdiploid + cases) while less than 10% of myeloma cells were hyperdiploid in five cases (hyperdiploid - cases). The proportion of hyperdiploid cells among all myeloma cells was highly correlated with incidence of myeloma cells with morphologically abnormal nuclei such as those with multiple-nuclei or convoluted nuclei (P = 0.001). Among the eight hyperdiploid + cases, two (2/8) showed good response to subsequent chemotherapy while four of five hyperdiploid - cases (4/5) responded well. Cases with poor response had more hyperdiploid myeloma cells (average 25.7% of all myeloma cells) than sensitive cases (average 6.8%), suggesting a contribution of hyperdiploid myeloma cells to primary drug resistance (P = 0.065). The 3 year survival rate of hyperdiploid+cases was 0% while that of the control group was 41.9%. These results suggest that myeloma cells with abnormal nuclear morphology may show hyperdiploidy and poor response to chemotherapy.

S‐Phase cells of the lymphoplasmocytic compartment in hyperdiploid multiple myeloma are diploid cells

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.