UMLS:C0026764 - FACTA Search

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Query: UMLS:C0026764 (multiple myeloma)
36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The peripheral blood lymphocytes from 42 patients with multiple myeloma (MM) and 13 patients with monoclonal gammopathy of undetermined significance (MGUS) were studied by three-color immunofluorescence (IF) using antibodies directed to a broad range of B-cell markers (CD19, CD20, CD21, CD24), CALLA (CD10), PCA-1 (a plasma cell marker), and to the high and low molecular weight isoforms of the leukocyte common antigen, CD45RA (p205/220) and CD45RO (p 180). CD45RA is expressed on pre-B and B cells, and a transition from CD45RA to CD45RO defines differentiation towards plasma cells. Peripheral blood mononuclear cells (PBMC) from patients with myeloma included a large subset of B-lineage cells (mean of 39% to 45%) that were CALLA+ and PCA-1+ in all patients studied, including newly diagnosed patients and patients undergoing chemotherapy. Southern blot analysis indicated the presence of monoclonal Ig rearrangements in PBMC and a substantial reduction in the germ-line bands consistent with the presence of a large monoclonal B-cell subset. Avoidance of purification methods involving depletion of adherent cells was essential for detection of the abnormal B cells. Phenotypically, this abnormal B-cell population corresponded to late B or early pre-plasma cells (20% to 80% of PBMC), as defined by the concomitant expression of low densities of CD19 and CD20, moderate densities of CALLA and PCA-1, and strong expression of CD45RO on all B cells, with weakly coexpressed CD45RA on a small proportion. Heterogeneity in the expression of CD45RA and CD45RO within the abnormal B-cell population from any given patient suggested multiple differentiation stages. Abnormal B cells similar to those in MM were also detected in MGUS, although as a lower proportion of PBMC (26%). Abnormal B cells from patients with MGUS expressed predominantly the CD45RO isoform, but had a lower proportion of CALLA+ and PCA-1+ cells than were found on B cells from MM. This work indicates that the large subset of circulating monoclonal B lymphocytes from myeloma patients are at a late stage in B-cell differentiation, continuously progressing towards the plasma cell stage.
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PMID:Selective expression of CD45 isoforms defines CALLA+ monoclonal B-lineage cells in peripheral blood from myeloma patients as late stage B cells. 183 May

Two IL-6-dependent human multiple myeloma cell lines, ILKM2 and ILKM3, were established from the bone marrow of patients with IgG-K multiple myeloma. Both cell lines had the typical morphology and immunocytochemical features of myeloma cells. The surface phenotype of both cell lines was PCA-1+, OKT10+, CD10(J-5)-, CD19(B4)-, CD20(B1)-, CD21(B2)-, and OKIa-1-. A monoclonal cytoplasmic Ig, IgG-K or K L chain, was positive in ILKM2 or ILKM3, respectively. EBV nuclear antigen was negative in both cell lines. They proliferated in the presence of macrophages or macrophage-derived factors (MDF). Among the recombinant cytokines examined, IL-6 most strongly augmented the growth of both cell lines. The anti-IL-6 antibody completely inhibited the IL-6-dependent growth and almost completely inhibited the MDF- or purified MDF-dependent growth of both cell lines, ILKM2 and ILKM3 are now being maintained in the culture medium containing 2 ng/ml rIL-6. These results suggest that IL-6 produced by macrophages may play an important role in the growth of myeloma cells in vivo and that macrophages or IL-6 can be used for establishing human myeloma cell lines.
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PMID:Establishment of two interleukin 6 (B cell stimulatory factor 2/interferon beta 2)-dependent human bone marrow-derived myeloma cell lines. 278 35

Two monoclonal antibodies (To15 and 4KB128) specific for the B cell-associated CD22 antigen (135,000 mol wt) are described. On immunoenzymatic analysis of cryostat tissue sections, these antibodies strongly label both mantle zone and germinal center B lymphoid cells in secondary lymphoid follicles (and also scattered extrafollicular lymphoid cells) but are unreactive with other cell types (with the exception of weak reactivity with some epithelioid histiocytes). These reactions differ from those of monoclonal antibodies B1 and B2 (anti-CD20 and CD21) but are similar to those of the pan-B antibody B4 (anti-CD19). One of the anti-CD22 antibodies (To15) has been tested extensively by immunoenzymatic labeling on greater than 350 neoplastic lymphoid and hematological samples. The CD22 antigen was found in tissue sections in most B cell-derived neoplasms, the major exceptions being myeloma (all cases negative) and a small proportion of high-grade lymphoma (6% of cases negative). In cell smears, the antigen could be found on neoplastic cells in most B cell lymphoproliferative disorders, including common acute lymphoblastic leukemia (ALL) (90% positive) and B cell chronic lymphocytic leukemia (CLL) (89% positive). We conclude that anti-CD22 antibodies are of value for identification of human B cell lymphoproliferative disorders (especially when used in conjunction with anti-CD19 antibodies). Previous reports that the CD22 antigen is absent from many B cell neoplasms are probably due to its being expressed within the cytoplasm of immature B cells rather than on their surface.
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PMID:Value of monoclonal anti-CD22 (p135) antibodies for the detection of normal and neoplastic B lymphoid cells. 310 66

A human myeloma cell line designated LOPRA-1 has been established from ascites fluid containing malignant plasma cells of a patient with IgA2/kappa multiple myeloma. The cultured cells which are Epstein-Barr virus (EBV) negative have retained the morphological, cytochemical, ultrastructural and immunophenotypical features of well-differentiated plasma cells. They express the plasma cell antigen PCA-1, the antigens CD28 (Kolt-2) and CD38 (OKT10), the transferrin-receptor (OKT9), and some epitopes of the CD24 antigen (HB8, VIB E3), but are negative for surface immunoglobulins. HLA class II antigens (HLA-DP, -DQ, -DR) and other B-cell markers such as CD10 (CALLA), CD19 (B4), CD20 (B1), CD21 (B2), CD22 (HD39), CD23 (MHM6), CD37 (BL14) and CD39 (G28-8) as analysed by both flow cytometry and immunocytochemistry (PAP/APAAP). With respect to immunoglobulin synthesis, two stable clones were selected by single cell cloning: clone LOPRA-1/5 synthesizes large amounts of alpha 2 heavy and kappa light chains, but secretes only small amounts of these molecules, whereas clone LOPRA-1/4 is clearly devoid of intracellular immunoglobulin heavy and light chains and thus appears to be a chain loss variant. Cytogenetic analysis revealed a pseudotriploid phenotype with several structurally abnormal marker chromosomes: 3n + -, 70, XX, -X, -1, -4, -6, -8, -8, -13, -16, +7, +18, +21, +i(1q), +i(1q), +6q-, +3mar.
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PMID:Establishment and characterization of a permanent human IgA2/kappa myeloma cell line. 313 91

A major problem in the study of peripheral blood (PB) B cells from patients with multiple myeloma (MM) is the distinction between the cells really able to synthesize membrane (m) immunoglobulins (Ig) and those able only to absorb serum Ig passively, since the lymphocytes of such patients are bathed in very high concentrations of monoclonal Ig. In order to reappraise PB B cells (including putative pre-B cells) in MM, we have used three different criteria: (a) the capacity of PB B cells to cap mIg when triggered by an anti-Ig; (b) the presence of B-cell differentiation antigens (CD19, CD20, CD21, and CD37) as specific B-cell markers; and (c) the expression of cytoplasmic mu heavy chain as a marker of pre-B cells. We have found that, in active myeloma (N = 13), the percentages and absolute numbers of PB B cells able to cap mIg (4.25%; 45.43 cells/mm3) were significantly lower than those in healthy donors (8.4%; 151.2 cells/mm3) and those in stable MM (7.67%; 134.39 cells/mm3). In addition, the capping formation in patients with stable or active MM was significantly delayed compared to that in healthy donors. For all the normal individuals and patients investigated, there has been found an excellent correlation between the percentages and absolute numbers of PB B cells able to cap their mIg and those of PB mononuclear cells bearing the four B cell-specific differentiation antigens: CD19, CD20, CD21, and CD37. Finally, virtually no pre-B cells bearing cytoplasmic mu chains have been identified in the peripheral blood from healthy donors and patients with MM.
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PMID:Delay and not deficiency in cap formation of peripheral blood B cells in patients with multiple myeloma. 313 44

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.
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PMID:Expression of CD21 antigen on myeloma cells and its involvement in their adhesion to bone marrow stromal cells. 778 Jan 54

A 12-year-old, female spayed Chihuahua was diagnosed with nonsecretory multiple myeloma on the basis of multiple osteolytic lesions, histological evidence of plasma cell infiltrate on a bone biopsy, and absence of a monoclonal protein on serum and urine electrophoresis. A 6-week course of prednisone therapy resulted in no clinical improvement and the dog was euthanized 2 weeks after presentation because of progressive neurological impairment. Bone marrow specimens were processed and stained for ultrastructural and immunohistologic evaluation. Staining with antisera to immunoglobulin (Ig) G, IgM, and IgA was negative. Tumor cells in both the pelvic and rib masses displayed prominent reactivity with an antibody specific for a canine beta 1 integrin similar to VLA-4; however, the tumor cells failed to stain with antibodies known to react predominantly with antigens on B-lymphocytes (major histocompatibility complex class II, CD45RA, and CD21) or T-lymphocytes (Thy-1). The tumor cells also failed to stain with an antibody specific for the beta-subunit (CD18) of the leukocyte integrins (D11/CD18). Ultrastructural studies performed on bone marrow specimens revealed a pleomorphic population of plasma cells with moderate amounts of rough endoplasmic reticulum, erythrophagocytosis, and lack of crystalline inclusions.
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PMID:Nonsecretory multiple myeloma in a dog: immunohistologic and ultrastructural observations. 789 63

The Australian Leukaemia Study Group myeloma study (MM1) aimed to determine the prognostic significance of clinical and immunophenotypic markers in patients with multiple myeloma. All patients were treated with standard dose melphalan and prednisone. Seventy-four patients were entered and the median survival was 27 months. Serum beta 2-microglobulin (beta 2M) and albumin levels were the only significant clinical factors influencing survival (p = 0.007 and p = 0.008, respectively). Patients with raised levels of CD38+ lymphocytes at presentation had a significantly shorter survival than patients with normal levels (p = 0.01, logrank test, median 19 months vs 33 months). CD38 antigen expression was independent of beta 2M but patients with raised levels of CD38 had significantly lower levels of albumin than patients with normal levels (p = 0.001) which may explain their poorer survival. Salmon and Durie stage was not associated with antigen expression. No other B-cell antigens (CD10, CD19, CD20, CD21, CD22, CD23, FMC1 or FMC7) or plasma cell antigens tested (PCA-1) were found to be associated with prognosis. Patients who achieved plateau phase had a better prognosis than those who did not (p = 0.04 in a landmark analysis). Patients who achieved plateau phase following an objective response appeared to have a better prognosis than those who were in plateau phase at presentation (p = 0.09 in a landmark analysis). Light chain isotype suppression (LCIS) was not associated with a significant survival advantage and did not correlate with any known prognostic indicator.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Peripheral blood lymphocyte surface antigen expression and prognosis in myeloma: Australian Leukaemia Study Group Study. 795 Sep 19

We report a novel, reproducible methodology which enabled 10 human myeloma cell lines (HMCL) to be obtained from each of 10 tumor samples harvested from 9 patients with extramedullary proliferation. Fresh samples were cultured with interleukin 6 (IL-6) and granulocyte macrophage-colony stimulating factor (GM-CSF) at a high cell density and resulting HMCL growth became progressively dependent on IL-6 alone, no longer requiring GM-CSF. These HMCL, which had the same immunoglobulin gene rearrangements as the patients' original myeloma cells, were designated XG-1 to XG-9. XG HMCL had a plasma cell morphology, expressed plasma cell antigen (Ag), namely cytoplasmic immunoglobulins, CD38, B-B4 Ag, and CD77, and lacked the usual B-cell Ag. They also expressed activation antigens such as CD28 with coexpression of CD28 and its ligand, B7 Ag, in four HMCL. Six HMCL expressed CD40, 4 CD23, and 5 its ligand, CD21. The XG HMCL bore adhesion molecules VLA-4 and CD44 (all 10 HMCL), VLA-5 (7 HMCL), and CD56 (4 HMCL). Finally, cytogenetic study of 8 HMCL indicated a 14q+ chromosome, and t(11,14) translocation was found in 6 of 8 and 5 of 8 HMCL, respectively. The possibility of obtaining malignant plasma cell lines reproducibly from each patient with extramedullary proliferation offers a unique tool for studying the phenotype and abnormalities of the still unidentified tumor stem cell in this disease.
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PMID:Reproducible obtaining of human myeloma cell lines as a model for tumor stem cell study in human multiple myeloma. 820 90

B cells differentiate into plasma cells which produce antibodies in the bone marrow (BM). Multiple myeloma (MM) is a hematologic malignancy in human plasma cells, and myeloma cells grow mainly in BM. According to phenotypic differences, such as expression of adhesion molecules, human myeloma cells as well as normal plasma cells can be classified into several differentiation stages. We have found that cells strongly expressing CD38 antigens (CD38++(+)) in BM are all plasma cells, and that there also are no plasma cells in either CD38- cell fraction or fraction of cells weakly expressing CD38 antigens (CD38+). Myeloma cells in BM consist of CD38++(+)MPC-1-CD49e (VLA-5)-immature and CD38++(+)MPC-1+CD49e+ mature myeloma cells. Immature myeloma cells proliferate markedly in vitro and respond to interleukin-6 (IL-6), a growth factor for myeloma cells, whereas mature myeloma cells show very low proliferative activities and show no response to IL-6. Immature myeloma cells expressing CD21 molecules on their surface seem to attach to stromal cells in BM through binding to CD23 molecules. Thus, there is a heterogeneity in human myeloma cells, and immature myeloma cells appear to proliferate in response to IL-6.
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PMID:Biological significance of heterogeneity in human myeloma cells. 988 36

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