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PubMed1993

P-glycoprotein expression in human plasma cell myeloma: correlation with prior chemotherapy.

Multidrug-resistant (MDR) myeloma patients failing chemotherapy may express P-glycoprotein (PGP), which serves as an efflux pump protecting the neoplastic cells. Unknown is whether PGP expression might relate to prior cytotoxic drug exposure. To address this question, we studied 106 consecutive bone marrow samples from 104 myeloma patients with samples studied either before or after therapy and at the time of relapse. We performed an established immunocytochemical assay of PGP using an MDR-1-specific monoclonal antibody and correlated PGP status with prior chemotherapy dosage. Myeloma patients with no prior therapy had a low incidence of PGP expression (6%, 3/47), whereas those receiving chemotherapy had a significantly higher incidence (43%, 21/49) (P < .0001). A substantially higher incidence of PGP expression (50%, 83%, respectively) occurred when the total vincristine dose exceeded 20 mg and when doxorubicin exceeded 340 mg. In the 11 patients who received both high vincristine and doxorubicin dosages (> 20 mg, > 340 mg total dose) there was 100% incidence of PGP expression in the tumor cells. These data provided the basis for a predictive mathematical model from which dose-related PGP expression normograms were generated. Time with myeloma for PGP-negative patients (mean 33 months) had overlapping confidence limits with PGP-positive patients (mean 42 months), suggesting that disease duration was not a significant variable. PGP expression did not correlate with other clinical factors or immunophenotypic factors. Our findings indicate a strong correlation between PGP expression in myeloma and past chemotherapy in myeloma, in particular, related to prior exposure to the natural product agents vincristine and doxorubicin. Additionally, the proportion of PGP-positive plasma cells was significantly higher in the doxorubicin-treated patients than the nondoxorubicin-treated patients (87.7% v 65.17%; P = .013). Combined high vincristine and doxorubicin total dosage appear highly predictive of PGP expression.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1993

Phenotypic difference of normal plasma cells from mature myeloma cells.

We have recently shown that two-color analysis with fluorescein isothiocyanate (FITC)-anti-CD38 antibody could clearly distinguish myeloma cells (plasma cells) from other hematopoietic cells in the bone marrow. Myeloma cells (plasma cells) alone were located at CD38strong positive (++) fractions. To further distinguish normal plasma cells from mature myeloma cells phenotypically, we examined immunophenotypes of normal plasma cells and myeloma cells by two-color flow cytometry with FITC-anti-CD38 antibody and phycoerythrin staining with antibody to VLA-4, MPC-1, CD44, CD56, CD19, CD20, CD24, or CD10. Normal plasma cells were all VLA-4+VLA-5+MPC-1+CD44+ CD19+CD56- in the bone marrows from seven healthy donors, tonsils from four patients with chronic tonsillitis, a spleen from one patient with idiopathic thrombocytopenic purpura, and lymph nodes from two patients with chronic lymphadenitis, respectively. On the other hand, mature myeloma cells (12 of 20 cases), VLA-4+VLA-5+MPC-1+, were all CD19- and most of them CD56+, and there were no myeloma cells with the CD19+CD56- phenotype in the 20 cases of myelomas we tested. Thus, as for the expression of CD19 and CD56, normal plasma cells from various tissues are all CD19+CD56-, whereas no myeloma cells have the CD19+CD56- phenotype. According to this finding, we investigated the expression of CD19 and CD56 on plasma cells (CD38++ fractions) in monoclonal gammopathy of undetermined significance (MGUS). Both CD19+CD56- and CD19-DC56+ plasma cells were found in all five cases of MGUS we tested, suggesting that MGUS consists of phenotypically normal plasma cells and myeloma cells. Therefore, it is reasoned that phenotypic analysis of plasma cells with anti-CD19 and anti-CD56 antibodies can distinguish normal plasma cells from malignant plasma cells (myeloma cells), and can detect malignant plasma cells even in MGUS or premyeloma states.

Aged↗
PubMed1993

Expression of syndecan regulates human myeloma plasma cell adhesion to type I collagen.

The syndecans comprise a family of integral membrane proteoglycans that regulate cell behaviors by binding to extracellular matrix and binding growth factors. In mouse blood cells, syndecan expression is restricted to cells of the B-cell lineage where it is expressed by pre-B cells and plasma cells, but is absent from circulating B cells. In the present study, we examined the expression, structure, and function of syndecan on human myeloma cell lines and myeloma patient bone marrow cells. On myeloma cells, syndecan is a small (modal relative molecular mass [M(r)] = 120 Kd) heparan sulfate proteoglycan localized at the cell surface. Syndecan was detected by immunodot blotting on 7 of 10 human myeloma cell lines and by reverse transcriptase polymerase chain reaction on 10 of 14 patient samples. Cell binding assays show that myeloma cells expressing syndecan bind to type I collagen via heparan sulfate chains, while those cell lines not expressing syndecan do not bind to collagen. Furthermore, the cell lines expressing syndecan were negative for CD19 and CD45 staining, indicating that syndecan expression is restricted to tumors having a well-differentiated phenotype. We conclude that syndecan acts as a matrix receptor on human myeloma cells but is not expressed by all tumors, suggesting that syndecan may participate in regulating myeloma cell adhesion to the bone marrow stromal matrix.

Cell Adhesion↗
PubMed1991

Paraproteinemic corneal deposits in plasma cell myeloma.

We treated two patients who had IgG-kappa-light chain monoclonal gammopathy with partially crystalline and partially amorphic corneal deposits. Impairment of vision made keratoplasty necessary for each patient. Histologic examination of the corneal specimens showed deposits that stained positively for Masson's trichrome in all corneal cells. Immunohistochemical tests identified these deposits as IgG-kappa-light chain immunoglobulin fragments. Electron microscopy showed intracellular, rhomboid-shaped deposits enveloped by a membrane. The same deposits appeared in the conjunctival epithelium, within subconjunctival fibrocytes, and in the plasma cells of the bone marrow. Immunoelectrophoresis showed IgG-kappa-light chain fragments in the blood serum, the lacrimal film, and the aqueous humor. This suggests that the intracellular immunoglobulin fragments may have entered the corneal and conjunctival epithelium by way of the lacrimal film, the keratocytes by way of the corneo-scleral limbus vasculature, and the endothelial cells from the aqueous humor.

Aged↗
PubMed1976

Clinically significant cardiac infiltration in acute leukemia, lymphocytic lymphoma, and plasma cell myeloma.

Cardiac infiltration by hematologic neoplasms leading to clinically significant cardiovascular disease is rare. Three such cases are described in this report, and it is suggested that rare manifestations of hematologic neoplasms may become more common in the future since these diseases are more amenable to therapy than heretofore. Cardiac involvement with hematologic neoplasms is of more than academic interest since this complication is likely to respond to radiotherapy.

Adult↗
PubMed1984

Anaplastic plasma cell myeloma and immunoblastic lymphoma. Clinical, pathologic, and immunologic comparison.

To test whether highly anaplastic myeloma and immunoblastic lymphoma are truly identical disease processes, simultaneous series were compared in respect to cytomorphologic features, immunoglobulin content or secretion, clinical and laboratory findings, and patient survival. Although the series partially overlapped in each studied feature, different trends served to distinguish them. Of the 14 patients with myeloma, all were dead at two years, whereas six of the 22 patients with lymphoma were disease-free at 35 to 78 months. Only 50 percent of patients with myeloma received intensive chemotherapy, whereas all 19 patients with stage III or IV lymphoma received such therapy. Myelomas secreted predominantly IgA heavy chain rather than IgG and lambda light chain rather than kappa. Lymphomas contained predominantly IgM rather than IgG and kappa rather than lambda. There were no IgM myelomas and no IgA lymphomas. The shorter survival of patients with the extremely anaplastic form of myeloma, as compared with patients who had immunoblastic lymphoma, may relate, in part, to prior therapy for previous lower grade myeloma; however, intrinsic differences in the nature of these two disease processes are reflected in their disparate immunologic characteristics.

Adult↗
PubMed1979

Ultrastructure of a plasma-cell myeloma in the mandible.

Tumor cells exhibited large amounts of rough endoplasmic reticulum arranged in a lamellar pattern, large numbers of mitochondria with a perinuclear distribution, and a prominent Golgi complex, but only a small number of immunoglobulin granules. No crystalline structures of immunoglobulins were observed. Nuclei exhibited patchy condensation of chromatin and large nucleoli. The ultrastructural features suggest that this case could be a "resecretory" myeloma.

Aged↗