Immature Myeloma Cells Research Articles

High proportions of VLA-5- immature myeloma cells correlated well with poor response to treatment in multiple myeloma.

Using two-colour phenotypic analysis with anti-CD38 antibody, human myeloma cells can be classified into VLA-5- immature and VLA-5+ mature cells. We examined the relationship between variations of these subpopulations and clinical responses during treatment in multiple myeloma (MM). 39 patients with MM were treated with combined chemotherapy. First estimation of clinical responses after induction therapy showed that early clinical responses were correlated with the percentage of immature myeloma cells present after induction therapy (P < 0.01), not at diagnosis. After three courses of cyclic maintenance therapy, immature myeloma cells significantly decreased in proportion along with a decrease in total myeloma cells in maintained or more responsive cases (P < 0.01). On the other hand, immature myeloma cells were still found in high proportions in nonresponsive cases with no change (NC) or minor response (MR) (P < 0.01). Furthermore, in relapsing cases from partial response (PR) or progressive disease (PD) from nonresponsive cases, immature myeloma cells increased markedly. Therefore these results show that high proportions of VLA-5- immature myeloma cells remaining after induction therapy and during maintenance therapy correlate well with a declining clinical course of MM during maintenance therapy.

Expression of CD21 Antigen on Myeloma Cells and its Involvement in Their Adhesion to Bone Marrow Stromal Cells

The mature myeloma cells express very late antigen 5 (VLA-5) and MPC-1 antigens on their surface and adhere to bone marrow (BM) stromal cells more tightly than the VLA-5-MPC-1- immature myeloma cells in vitro. The VLA-5 and MPC-1 antigens possibly function as two of the molecules responsible for interaction of mature myeloma cells with BM stromal cells. However, the immature myeloma cells do interact with BM stromal cells, and it is unclear which adhesion molecules mediate their interaction. In this study, we found that both immature and mature myeloma cells expressed CD21, an adhesion molecule known to bind to CD23. CD21 was also detected on normal plasma cells. To evaluate the role of CD21 expression on myeloma cells, two myeloma cell lines, NOP-2 (VLA-5-MPC-1-) and KMS-5 (VLA-5+MPC-1+), were used as representatives of immature and mature myeloma cell types, respectively, and an adhesion assay was performed between the myeloma cell lines and BM stromal cells. Antibody-blocking results showed that adhesion of the mature type KMS-5 to KM102, a human BM-derived stromal cell line, or to short-term cultured BM primary stromal cells was inhibited by monoclonal antibodies (MoAbs) against CD21, VLA-5, and MPC-1, and inhibition of adhesion of the immature type NOP-2 to KM102 by the anti-CD21 MoAb was observed as well. Furthermore, CD23 was detected on KM102. Treatment of KM102 with an anti-CD23 MoAb also inhibited adhesion of either KMS-5 or NOP-2 to KM102. Therefore, we propose that CD21 expressed on myeloma cells likely functions as a molecule responsible for the interaction of immature myeloma cells as well as mature myeloma cells with BM stromal cells, and CD23 may be the ligand on the stromal cells for the CD21-mediated adhesion.

A new phenotypic classification of bone marrow plasmacytosis.

Here, we propose a new phenotypic classification of bone marrow plasmacytosis. By 2-color phenotypic analysis with FITC anti-CD38 and PE anti-CD19, -CD56, -VLA-5 or MPC-1 antibody, plasma cells are easily identified on the histogram, even though no more than 1% of plasma cells are found in the bone marrow. Hence, plasma cells are phenotypically classified into polyclonal (reactive) (CD19+CD56-) or monoclonal (neoplastic) plasma cells (mostly CD19-CD56+), and furthermore immature (VLA-5-MPC-1-), intermediate (VLA-5-MPC-1+) and mature plasma cells (VLA-5+MPC-1+). According to these findings, plasmacytosis in the bone marrow can be classified into polyclonal marrow plasmacytosis (POMP) and monoclonal marrow plasmacytosis (MOMP) states. The MOMP state is further subclassified into MOMP-1 and MOMP-2, MOMP-3 and MOMP-4; MOMP-1 is defined by co-existence of monoclonal plasma cells and polyclonal plasma cells, and MOMP-2 to MOMP-4 are dependent on increased proportions of VLA-5-MPC-1- immature myeloma (plasma) cells. We found that the cases of benign monoclonal gammopathy (BMG) according to the conventional classification were in the MOMP-1 state, and myelomas could be classified into the MOMP-2 to MOMP-4 state. Subclassification of the MOMP state may be useful in determining the prognosis of myelomas, where an increase in immature myeloma cells is reported to correlate well with their aggravation during the clinical courses. Therefore, this new phenotypic classification of bone marrow plasmacytosis (POMP and MOMP-1 to MOMP-4) will contribute to differential diagnosis and understanding of therapeutic responses and prognosis in myelomas.

The many facets of multiple myeloma

M ULTIPLE MYELOMA is a neoplastic proliferation of plasma cells, generally originating in the bone marrow. These globulin-producing plasma cells may be immature (myeloma cells). Most of the clinical features are due to marrow infiltration and bone destruction by plasma cells. Multiple myeloma is most common in patients between 45 and 70 yr of age. The disease is characterized by bone pain, particularly in the back (with or without pathologic fracture), weakness, soft-tissue masses, renal insufficiency, neurologic symptoms, and frequent infections.“r6 Abnormal laboratory findings include anemia, hyperglobulinemia, hypercalcemia and hyperuricemia. The alkaline phosphatase is typically normal in uncomplicated cases. Serum or urine electrophoresis shows a characteristic M-type protein peak, and bone marrow study reveals an increase in plasma or myeloma cells.24 The natural history of myeloma is undergoing constant study.” The abnormal electrophoretic changes and even plasma cell proliferation in the marrow may be present for a long period before clinical or radiologic evidence of disease is found. Radiographically, the typical myeloma shows multiple small osteolytic lesions with sharp punched-out margins (Fig. 1). However, the roentgen appearance is extremely variable (Table l), and these variations will be emphasized in the following discussion.