Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The immunophenotypic features of lymphoid leukemias and non-Hodgkin's lymphomas are reviewed. Emphasis is placed on the more recent literature, particularly the insights provided by monoclonal antibodies specific for T and B lymphocytes, and the contributions of flow cytometry. Characteristic immunophenotypes for T- and B-lineage acute lymphoblastic leukemia, the non-Hodgkin's lymphomas, chronic B- and T-cell lymphoproliferative disorders, and multiple myeloma are described. The importance of this information in the diagnostic process and in providing prognostic information concerning disease progression is considered. Limitations associated with monoclonal antibody reagents and flow technology are noted. Representative panels of monoclonal antibodies as used in the author's laboratory for characterizing these disorders are presented and discussed in light of the author's experience.
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PMID:Membrane antigen analysis in the diagnosis of lymphoid leukemias and lymphomas. Differential diagnosis, prognosis as related to immunophenotype, and recommendations for testing. 265 5

Beta 2 microglobulin is a low molecular weight protein integrating the light chain HLA antigens. Its serum concentration is increased in different neoplasias and in renal failure. Using solid phase RIA we determined the concentration of beta 2 microglobulin in plasma and spinal fluid of 57 healthy individuals and patients with hematologic neoplasia. Serum levels were 1.34 +/- 0.34 mg/l and spinal fluid levels were 1.3 +/- 0.7 mg/l in healthy subjects. Serum levels in 29 patients with myeloma was 7.51 mg/l, significantly higher in those with renal failure (12.35 mg/l) compared to those without (4.54). In 30 patients with non-Hodgkin lymphoma the mean serum levels were 2.90 mg/l, significantly greater in those with active disease (3.18) than in those with remission (1.5). No difference was found according to the degree of malignancy. Patients with acute lymphatic leukemia had elevated values of beta 2 microglobulin while the disease was active (3.37 mg/l), decreasing to normal levels after remission (1.79 mg/l). Spinal fluid levels of beta 2 microglobulin were elevated only in patients with central nervous system involvement. Our results indicate that serum levels of beta 2 microglobulin are helpful in patients with hematologic neoplasia in assessing the activity of the disease and tumor mass, especially in multiple myeloma.
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PMID:[Beta 2 microglobulin in some hematologic neoplasms]. 266 40

Five human myeloma cell lines, KMM-1, KMS-5, KMS-11, KMS-12-PE, and KMS-12-BM, have been established at Kawasaki Medical School since 1980. As the KMS-12-PE and KMS-12-BM lines were obtained from the same patient, these five cell lines have been derived from four patients with multiple myeloma. The five myeloma cell lines are stably growing at present in RPMI 1640 medium supplemented with 10% fetal bovine serum. They can also grow in a defined culture medium without serum. That these cell lines were human myeloma cells was confirmed by the following findings. Ultrastructurally, all five cell lines showed features characteristic of plasma cells. KMM-1 and KMS-11 cells secreted lambda and kappa chains into the culture medium, respectively, but the other cell lines produced no immunoglobulins. KMM-1 expressed cytoplasmic lambda antigen, KMS-5 showed cytoplasmic delta, and KMS-11 expressed surface kappa, whereas KMS-12-PE and KMS-12-BM cells showed no surface or cytoplasmic immunoglobulins. Regarding reaction with a monoclonal plasma cell antibody (PCA-1), four of the five lines were positive, the exception being KMS-5. Another monoclonal antibody (CD38), which also recognizes plasma cells, responded to KMM-1, KMS-12-PE, and KSM-12-BM. KMS-5 cells expressed acute lymphoblastic leukemia antigens (CALLA). These data suggest that such lines as KMM-1, KMS-11, KMS-12-PE, and KMS-12-BM represent later stages of B-cell differentiation, and that KMS-5 represents a relatively early stage of B-cell differentiation. All the cell lines lacked Epstein-Barr virus nuclear antigen, showed abnormal karyotypes of human origin, and differed from each other in the isozyme patterns examined. Only KMS-5 was tumorigenic when transplanted subcutaneously into nude mice.
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PMID:Establishment of five human myeloma cell lines. 276 32

Suppression of the green fluorescence of acridine orange by 5-bromodeoxyuridine incorporation into cellular DNA was measured by flow cytometry. Bone marrow cells from normal volunteers and patients with chronic myelogenous leukemia acute lymphocytic leukemia acute myelogenous leukemia and multiple myeloma were incubated with BUdR in vitro. By 24 h acridine orange stained cycling cells that had synthesized DNA in the presence of BUdR were differentiated from quiescent cells as a second peak with quenched green fluorescence (DNA). After 72 h in culture 11-65% of the G0/G1 cells from normal bone marrows and bone marrows with myeloid leukemia were identified as cycling in culture by the presence of a second peak with quenched green fluorescence. A greater percentage of cells with BUdR quenched AO fluorescence was associated of acridine orange was higher in the cycling cells that had synthesized DNA in the presence of BUdR than in the non-cycling G0/G1 cells. In one patient with AML there was quenching of the DNA fluorescence of the aneuploid population but not the diploid population indicating that the aneuploid leukemia cells were proliferating. In contrast in patients with multiple myeloma, the quenched fluorescence of the diploid cell population and not the aneuploid cells, indicated that the diploid cells were proliferating. The cells from patients with untreated ALL failed to proliferation prohibiting an in vivo assessment of growth. Although measurements of proliferation obtained by this method are clearly influenced by the cell's adaptation to culture, measurement of BUdR quenching of acridine orange fluorescence is technically feasible and can identify and allow characterization of the cycling population of cells.
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PMID:5-bromodeoxyuridine (BUdR) quenching of acridine orange fluorescence distinguishes cycling and non-cycling normal and malignant bone marrow cells in vitro. 279 84

Four cases of plasma cell leukemia (PCL) are reported that illustrate the variable immunotype of this disorder in contrast with the immunologic profile described for normal B-cell maturation and typical multiple myeloma (MM). Mature B-lymphocytes express B1 antigen (Ag) and surface immunoglobulin (SIg) whereas maturation to the plasma cell stage is accompanied by loss of these immunologic markers and expression of T10 Ag, plasma cell Ag (PCA), and cytoplasmic immunoglobulin (CIg). Plasma cells from patients with MM have previously been found to express the immunophenotype of normal plasma cells. In contrast, none of the four cases reported here express an immunologic profile typical for specific B-cell differentiation stages. Only one of four cases was strongly positive for PCA but additionally expressed B1 Ag and SIg. Of the remaining three cases, all expressed T10 Ag and CIg; two cases also expressed SIg, weak PCA, and B1 Ag. All four cases were monoclonal for lambda light chains and negative for common ALL Ag (CALLA). The variable expression of mature B-cell markers and plasma cell markers demonstrates the immunophenotypic spectrum of PCL; the prognostic significance of this heterogeneity needs to be more closely examined.
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PMID:Immunophenotypic spectrum of plasma cell leukemia. 291 94

Peripheral blood mononuclear cells from a patient with chronic myelogenous leukemia (CML), in remission, were depleted of CD8-positive T-cells and cultured with Epstein-Barr virus. Four of 20 cultures (20%) secreted human IgG antibodies selectively reactive with the cell surfaces of certain human leukemia cell lines. Three polyclonal, Epstein-Barr virus-transformed, B-cell lines were expanded and fused with the human-mouse myeloma analogue HMMA2.11TG/O. Antibody from secreting clones HL 1.2 (IgG1), HL 2.1 (IgG3), and HL 3.1 (IgG1) have been characterized. All three react with HL-60 (promyelocytic), RWLeu4 (CML promyelocytic), and U937 (monocytic), but not with KG-1 (myeloblastic) or K562 (CML erythroid). There is no reactivity with T-cell lines, Burkitt's cell lines, pre-B-leukemia cell lines, or an undifferentiated CML cell line, BV173. Leukemic cells from two of seven patients with acute myelogenous leukemia and one of five with acute lymphocytic leukemia react with all three antibodies. Normal lymphocytes, monocytes, polymorphonuclear cells, red blood cells, bone marrow cells, and platelets do not react. Samples from patients with other diverse hematopoietic malignancies showed no reactivity. Immunoprecipitations suggest that the reactive antigen(s) is a lactoperoxidase iodinatable series of cell surface proteins with molecular weights of 42,000-54,000 and a noniodinatable protein with a molecular weight of 82,000. Based on these data these human monoclonal antibodies appear to react with myelomonocytic leukemic cells and may detect a leukemia-specific antigen or a highly restricted differentiation antigen.
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PMID:Human monoclonal antibodies reactive with human myelomonocytic leukemia cells. 292 15

In the majority of 188 non-Hodgkin lymphomas (NHL) investigated in this study, we found a simultaneous expression of the receptors for c3b and c3d (CR1 & CR2; cccorr = 0.69, P less than 0.0005). An analysis of the different histological entities of the Kiel classification revealed that this coexpression was most pronounced for germinal centre-derived (cccorr = 0.63, P = 0.0004) and immunocytic NHL (cccorr = 0.86, P = 0.0024), whereas in chronic lymphocytic leukaemias there tended to be a more heterogeneous pattern of complement receptor (CR) expression (cccorr = 0.29, P greater than 0.10). In contrast to these NHL of mid B cell stage, most of the NHL of early (i.e. acute lymphocytic leukaemia, lymphoblastic NHL) and late B cell stage (i.e. hairy cell leukaemia, immunoblastic NHL, multiple myeloma) did not express either of these receptors. CR positive NHL often showed a follicular arrangement of the neoplastic cells and had higher numbers of T helper/inducer (T4) lymphocytes (PCR1 less than 0.00005, PCR2 less than 0.05). Some cases of mid B cell NHL and all cases of hairy cell leukaemia reacted with antibodies against CR3 (i.e. the ic3b receptor).
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PMID:Receptors for the third component of complement: their association with maturation stage in non-Hodgkin lymphomas (NHL) and their possible implication with the development of follicular structures. 294 42

This study describes the presence of small numbers of common acute lymphocytic leukaemia antigen (CALLA, CD10)-positive lymphocytes in the peripheral blood of patients with multiple myeloma. A significant correlation (0.001 less than P less than 0.01) was found between the lack of light chain isotype suppression (LCIS), which is characteristic of progressive myeloma, and the presence of CALLA-positive lymphocytes. Sixty patients with multiple myeloma, four with benign monoclonal gammopathy (BMG) and seven with solitary plasmacytoma (SP) were monitored in this study. Nineteen of the patients with multiple myeloma demonstrated LCIS, of which only three were found to have CALLA-positive lymphocytes. Of the 41 patients with multiple myeloma who did not have LCIS, 20 (49%) had CALLA-bearing lymphocytes. None of the patients with BMG or SP demonstrated LCIS or were found to have CALLA-bearing lymphocytes in their blood. Forty-four of the patients with multiple myeloma were also monitored for serum beta-2-microglobulin (SB2M levels. There was no correlation between the SB2M and either LCIS or CALLA-positivity. Detection of CALLA-positive lymphocytes in the blood of patients with multiple myeloma may be an early marker of the onset of progressive disease. The correlation of CALLA expression on lymphocytes with lack of LCIS provides further evidence for the operation of immunoregulatory systems in these patients.
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PMID:Multiple myeloma: the relationship between CALLA (CD10) positive lymphocytes in the peripheral blood and light chain isotype suppression. 295 9

Human cell lines established from cases of acute lymphoblastic leukemia, lymphosarcoma, Burkitt's lymphoma and multiple myeloma and representing stages of B-lymphocyte development ranging from pre-B through to plasma cells, were assessed for their ability to produce and respond to B-cell growth factors (BCGF). All B-cell lines studied were found to be constitutive producers of a growth activity which assisted the S-phase entry of normal activated B-cells and provided growth support for lymphoblastoid cells transformed by Epstein-Barr virus. Furthermore, all lines responded by enhanced proliferation to supernatants from a BCGF-producing T-cell hybridoma. Not all lines, however, displayed autostimulation to their own supernatants and no tumor B-cell line appeared totally dependent on soluble factors for its growth. Non-tumorigenic B-cell lines, by contrast, revealed a strict dependency on homologous growth factor for their continued proliferation in suspension culture. The findings support a progression model of lymphomagenesis based upon the utilization, production and, ultimately, emancipation from growth-promoting soluble factors.
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PMID:Capacity of B-lymphocytic lines of diverse tumor origin to produce and respond to B-cell growth factors: a progression model for B-cell lymphomagenesis. 298 45

Epstein-Barr virus (EBV) can induce a broad spectrum of hematological diseases, especially in immune deficient patients. We assayed for receptor for EBV (EBVR) using fluoresceinated viral particles on 44 human hematopoietic cell lines derived from patients with T, B, and non-T, non-B acute lymphocytic leukemia (ALL), non-lymphoid leukemia, Burkitt lymphoma, myeloma and several unique lines we and others have recently developed. All 31 EBV nuclear-associated antigen (EBNA) negative cell lines were of neoplastic origin. Seven of 13 EBNA-positive cell lines were of normal cell origin. Four of 25 non-B (surface immunoglobulin negative) EBNA-negative neoplastic cell lines were EBVR-positive. Three of six EBNA-negative B-cell (surface immunoglobulin positive) lines were EBVR-positive. Nine of 13 EBNA-positive Burkitt and non-Burkitt cell lines strongly expressed EBVR. Four EBNA-positive Burkitt lymphoma cell lines exhibited EBVR only to a limited degree. Studies of the cell lines for EBVR, complement receptors (CR) and surface immunoglobulin (SIg) revealed that presence of SIg does not obligate the presence of EBVR. Functional EBVR accompanied SIg among EBNA-negative cell lines. SIg-negative cell lines can possess EBVR. Fourteen of 16 EBVR-positive lines were also positive for CR. The EBVR assay is a useful tool for assessing the potential role of EBV in the induction of hematopoietic disorders.
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PMID:Catalogue of Epstein-Barr virus (EBV) receptors on human malignant and non-malignant hematopoietic cell lines. 298 80


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