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

The phenotypic expression of Russell bodies (RB) in the tumor cells of two patients with different types of B-cell lymphoma and of one patient with plasma cell myeloma were examined. In both B-cell lymphomas, the RBs reacted consistently with anti-Leu 8 and anti-immunoglobulin M. The RBs in one case also reacted with other monoclonal antibodies, including anti-CD5, CD19, CD22, and CD25. The membranes of most of the tumor cells containing RBs did not stain. In the myeloma, the RBs reacted only with anti-immunoglobulin, and the myeloma cells expressed no surface antigens associated with B lymphocytes. This finding suggests that RBs do not form in cells that can transport glycoproteins to the cell membrane, but rather occur as a result of defective transport or process of certain glycoproteins by plasmacytoid cells.
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PMID:Russell bodies consist of heterogenous glycoproteins in B-cell lymphoma cells. 131 69

The 4D1D4 hybridoma cells were derived from the fusion of spleen cells from BALB/c nude mice with NS-1 mouse myeloma cells. The surface phenotypes of 4D1D4 hybridoma cells were Thy-1.2+, L3T4 (CD4)-, Lyt-2 (CD8)-, Asialo GM1+ and p-55 interleukin-2 (IL-2) receptor (CD25)-. This phenotypic pattern was consistent with the surface phenotype of NK cells. The 4D1D4 cells showed the definite killer activity against a syngenic tumor cell line, RL male-1, but not against an allogenic YAC-1 line. The killer activity of the 4D1D4 cells was not affected by the addition of exogenous IL-2. It was, therefore, suggested that 4D1D4 cells might be representative of resting NK cells with expression of no functional IL-2 receptors. The hybridoma technology might be useful for establishment of the cloned NK cells.
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PMID:Establishment of hybridoma cells with natural killer(NK)-like activity against syngenic tumor cells. 140 67

Lymph node cells from a patient with Hodgkin's disease (HD) were cultured without Epstein-Barr virus (EBV) or leukine adjuvant. A cell line (719-AB) emerged from the culture after four weeks. The cell line express CD20 (79%), CD 21 (30%), CD30 (63%), CD 35 (61%) antigens and weakly CD25 (19%). using Southern Blot technique, the existence of specific EBV DNA and polyclonal immunoglobulin genes rearrangement were observed in the cell line. In order to obtain a monoclonal antibodies (MoAb), mice Balb/C were immunized with this cell line. The splenic cells suspension of immunized animals were fused with the mouse myeloma NS1. Antibody IgM kappa from secreting clones 2B44 was studied using both indirect immunofluorescence with labeled anti-mouse immunoglobulin and immunohistochemistry based on alkaline phosphatase/antiphosphatase complex (APAAP) and ModAMeX technique on a panel of normal or pathological cells. Normal peripheral lymphocytes, monocytes, polymorphonuclear cells, and erythrocytes, did not react. The MoAb 2B44 recognized the dendritic reticulum cells and the smooth muscle cells of vessels on frozen section and paraffin section from HD or reactive lymph nodes. On specially processed paraffin sections (ModAMeX) Reed-Sternberg cells (RSC) were reactive with 2B44 MoAb (in 2 cases out of 5 tested). The molecular weight of the antigen recognized by 2B44 MoAb is of 37 kd. The description of a new epitope shared by different histological components might be of interest for defining a new cluster and better understanding the nature of RSC.
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PMID:Production of a monoclonal antibody (2B44) reactive on a shared epitope on dendritic reticulum cells, smooth muscle cells of vessels and Reed-Sternberg cells. 172 34

Cellular immunity was investigated in 43 patients with multiple myeloma (MM) by assessing 3HTdR uptake induced by monocyte-dependent [CD3 monoclonal antibodies (MoAbs), phytohemagglutinin (PHA)] and monocyte-independent (CD2 MoAbs, ionomycin + phorbolester) stimulations. The former were evaluated in peripheral blood mononuclear cells (PBMNC) and purified T cells; the latter were evaluated in purified T-cell preparations only. MM showed significantly lower PBMNC responses to PHA (P less than .001), soluble OKT3 (CD3) (P = .01), and immobilized OKT3 MoAbs (P = .01). On purification of T cells, MM responses were still defective to soluble T11(2) + T11(3) (CD2) MoAbs (P = .004), phorbol myristate acetate (PMA) plus ionomycin (P less than .001), but significantly higher to plastic-immobilized OKT3 (P = .004). In some MM, 3HTdR uptake, interleukin-2 (IL-2) receptor (CD25) expression, and IL-2 production were as high on stimulation with plastic-immobilized OKT3 as that observed in normal subjects under optimal conditions (ie, plastic-immobilized OKT3 plus accessory signals). CD3 hyperreactivity correlated with the number of CD8+ HLA-DR+ cells in MM T-cell preparations. MM patients with more than 10% CD8+ HLA-DR+ cells had significantly higher responses to immobilized OKT3 (P less than .001), but lower responses to T11(2) plus T11(3) (P = .01), and PMA plus ionomycin (P = .03) than patients with less than 10% CD8+ HLA-DR+ cells. Phenotyping of CD45RA (naive) and CD45R0 (memory) expressions in resting MM T cells showed a lower ratio of CD45RA to CD45R0 in both CD4 (P less than .05) and CD8 (P less than .001) subpopulations. These data indicate that (a) some MM T cells require significantly fewer accessory signals (if any) to express the IL-2 receptor fully, secrete IL-2, and proliferate on multivalent cross-linking of the CD3/TCR complex; and (b) this peculiar state of activation is associated with high HLA-DR expression in CD8+ lymphocytes.
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PMID:Detection of hyperreactive T cells in multiple myeloma by multivalent cross-linking of the CD3/TCR complex. 156 45

We have recently demonstrated that the CD24 antigen density of bone marrow (BM) lymphoid cells discriminates between pre-B cells and mature B-cells. Using this new method, we evaluated the B-cell lineage in the BM and peripheral blood (PB) of 18 patients with multiple myeloma (MM). First, the percentage of pre-B cells was significantly reduced by 40% in the BM of patients with MM: 2.3% +/- 2.2% versus 5.7% +/- 2.8% of normal BM lymphoid cells (P less than 0.01). This finding was associated with a significant reduction (50%) of the percentage of mature B-cells in both BM and PB, especially in patients with progressive disease (P less than 0.05). In contrast to what has been reported previously, we have not found any pre-B cells in the PB of these patients with MM. Secondly, BM pre-B and B-cell patients with MM did not express any activation markers (CD23, CD25, or CD71 antigens) and no CD5+ B-cells were found in the BM unlike in PB (8% CD5+ B-cells). Taken together, these data do not support the concept of a direct involvement (i.e, expansion or activation) of pre-B cells in MM without excluding the possibility of an early oncogenic event at the pre-B cell stage. Furthermore, our data emphasize this important reduction of the B-cell compartment (including that of pre-B cell) as a major cause of the humoral immunodeficiency in MM.
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PMID:No expansion of the pre-B and B-cell compartments in the bone marrow of patients with multiple myeloma. 190 6

We describe a new, spontaneously occurring BALB/c-derived murine T-cell leukemia. The leukemic cells, designated LB, grow rapidly and progressively in the syngeneic host with no signs of effective immunological resistance. LB cells expressed the Thy-1+, Lyt-2+, L3T4-, CD3- class-I+, CD25+ (IL-2 receptor, IL-2R), class-II-, gp70- phenotype. As LB cells express IL-2, as indicated by staining with 2 distinct anti-CD25 IL-2R monoclonal antibodies (MAbs), the therapeutic efficacy of IL-2-diphtheria toxin-related protein was tested on this leukemic model. IL-2-diphtheria toxin, but not diphtheria toxin, efficiently inhibited the proliferation of LB cells. The proliferation of a murine myeloma cell line, which does not express IL-2R, was not inhibited by IL-2-diphtheria toxin. The possible implantation of this animal model in fundamental and practical studies is discussed.
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PMID:Murine spontaneous T-cell leukemia constitutively expressing IL-2 receptor--a model for human T-cell malignancies expressing IL-2 receptor. 229

Activated killer cells, unrestricted by major histocompatibility (MHC) antigens circulate in the peripheral blood of patients who have undergone autologous and allogeneic bone marrow transplant (BMT) and may contribute to the reduced risk of leukemic relapse observed after these procedures. Interleukin-2 (IL-2) in vitro augments this cytotoxicity and used therapeutically might thereby promote the eradication of minimal residual disease. In order to assess whether these effects on cytotoxicity can be reproduced in vivo, we studied changes in number, phenotype, and MHC unrestricted cytotoxicity of peripheral blood mononuclear cells obtained from patients with hematologic malignancy receiving IL-2 infusions. Patients with acute myeloid leukemia and multiple myeloma were treated after cytotoxic chemotherapy or autologous BMT. IL-2 infusions produced an initial lymphopenia, followed by a progressive recovery in mononuclear cell numbers and a rebound lymphocytosis after the termination of treatment. This affected all lymphocyte subsets; in particular CD25 (IL-2 receptor) positive cell numbers rose sevenfold. Cells with the ability to kill a natural killer (NK)-resistant, lymphokine activated killer cell (LAK)-sensitive target appeared in the circulation during 16 of 19 infusions and mean LAK activity rose from 5.9% to 15.5% during infusion (E:T ratio, 50:1; P less than .001). During IL-2 infusion, cells present in the peripheral blood inhibited the growth of myeloid leukemia blasts in agar after overnight co-culture. Depletion experiments showed that LAK activity was mediated by cells of both CD3- CD16+ (NK derived) and CD3+ CD16- (T derived) subsets. LAK precursor activity in peripheral blood also significantly increased during IL-2 infusion. Increases in major histocompatibility complex (MHC) unrestricted cytotoxicity can be produced by IL-2 infusions in vivo and may result in improved relapse-free survival following chemotherapy or BMT.
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PMID:Effects of recombinant interleukin-2 administration on cytotoxic function following high-dose chemo-radiotherapy for hematological malignancy. 280 69

Seven independent cell lines were derived from the fusion of migratory cells recovered from explant cultures of metrial glands to SP 2/0, a non-Ig secreting B cell myeloma. The migrating cells came from a pool of metrial glands from day 6-8 pregnant random bred CD1 mice and were assumed to be cells early in the differentiation pathway to granulated metrial gland (GMG) cells. The fused cells were cloned twice at the limiting dilution. Hybridization was confirmed by quantitation of cellular DNA using propidium iodide staining and by karyotyping. Electron microscopy revealed that each of the hybrid cell lines was composed of cells which were lymphoid in appearance, but lacked the granules found in mature GMG cells. The surface phenotype of all lines is CD45+, LGL-1-, asialo GM-1-, IgG-, IgM-, CD3- and CD25- (p55 of IL-2 receptor). Although the hybridomas lack those phenotypic markers which were used to show that GMG cells are related to the natural killer (NK) cell lineage (ie LGL-1, asialo GM-1), they do express the pan-leukocyte marker CD45 as well as the lytic protein, perforin, at levels intermediate to those of SP 2/0 cells and GMG cells. In addition, the hybridomas were observed to preferentially bind the NK target cell YAC and to be capable of lytic activity at temperatures below 30 degrees C. Because these hybridomas may represent fusion to an early progenitor cell of the NK/GMG cell lineage, their continued characterization is of merit.
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PMID:Preliminary characterization of lymphoid hybridoma cell lines derived from the pregnant mouse uterus. 780 68

In vitro data have demonstrated autologous T-lymphocytes with anti-tumour activity in multiple myeloma (MM). Therefore a phase I/II trial was conducted to study the feasibility, the effect on several immunological parameters, and the tumour response induction of low-dose recombinant interleukin-2 (rIL-2) in MM patients. 18 MM patients of advanced stages in progress, who had failed on standard chemotherapy received 9 x 10(6) IU/m2 rIL-2 twice daily on days 1 and 2 and 0.9 x 10(6) IU/m2 twice daily for 5 subsequent days per week subcutaneously from days 3 to 56 (repeated every 12 weeks until progression). Patients were treated for between 8 and 1086 + d (mean 241 d) without serious side-effects. 6/17 patients experienced tumour response (2/17 objective tumour mass reduction, 4/17 long-lasting stable disease following tumour progression before initiation of rIL-2 treatment). During therapy the number of eosinophils increased 15-fold, CD4+ T lymphocytes were activated as demonstrated by enhanced CD25 antigen expression, and CD56+ NK cells expanded in the peripheral blood. Furthermore, a diminished pre-treatment ratio of CD4+/CD8+ lymphocytes was normalized during rIL-2 treatment. NK cell activity and lymphokine activated killer (LAK) cell activity was significantly enhanced. Endogenous IL-2 production and elevated soluble IL-2 receptor serum concentrations were induced. Low-dose rIL-2 can stimulate immune enhancement in MM despite the characteristic tumour-induced immunodeficiency. The treatment has proven though limited efficacy in advanced MM. Because most of the responders experienced termination of tumour progression rather than tumour regression, rIL-2 maintenance of chemotherapy-induced remissions should be investigated.
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PMID:Low-dose recombinant interleukin-2 therapy in advanced multiple myeloma. 787 83

We measured the soluble (s) receptors CD23, CD8, CD4, interleukin-2 receptor (IL-2R, CD25), and transferrin receptor (TfR, CD71), in normal serum and in patients with chronic lymphocytic leukemia (CLL) and evaluated them in relation to clinical and biological parameters of the disease, as well as serum immunoglobulin E (IgE). Compared to 31 normal individuals, 42 CLL patients had increased levels of sCD23 (98.4 +/- 127.7 versus 0.9 +/- 0.3 U/ml, p < 0.001), sIL-2R (6080 +/- 7030 versus 1420 +/- 640 pg/ml, p < 0.001), sTfR (12,100 +/- 11,250 versus 5000 +/- 1050 ng/ml, p < 0.001), and sCD8 (510 +/- 191 versus 234 +/- 89 U/ml, p < 0.001), but normal sCD4 levels. Mean sCD23 levels remained normal in patients with non-Hodgkin's lymphoma (other than small lymphocytic), Hodgkin's disease, hairy cell leukemia, acute lymphoblastic leukemia (ALL), acute myelogenous leukemia (AML), chronic myelogenous leukemia (CML), multiple myeloma, or solid tumors. Advancing Rai clinical stage was associated with a progressive elevation of sCD23 (p < 0.001), while sCD8 (p < 0.05), sIL-2R (p < 0.001), and sTfR (p < 0.005) were highest in stage 2 patients. Discriminant analysis confirmed the value of soluble receptor determinations in the clinical evaluation of CLL patients. sCD23 correlated with sIL-2R (p < 0.001) and sTfR (p < 0.05) but not with sCD4 or sCD8, and displayed an inverse relationship with serum IgE (NS) and total gamma-globulin (p < 0.05). sIL-2R correlated with sCD23 (p < 0.001), sTfR (p < 0.001), sCD4 (p < 0.01), and sCD8 (p < 0.01). The lymphocyte count correlated with serum lactate dehydrogenase (LDH) (p < 0.05), sCD23 (p < 0.001) and sIL-2R (p < 0.01) but not sTfR, sCD8, or sCD4. Chemotherapy produced consistent reductions of sCD23 levels in two responding patients. We conclude that: (i) sCD23 is considerably elevated in CLL, correlates with the tumor mass and clinical stage, and could be helpful in monitoring these patients; and (ii) sIL-2R, sCD8, and sTfR levels are less specifically increased and could be influenced by other factors such as immune activation and erythropoiesis.
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PMID:Soluble CD23 and other receptors (CD4, CD8, CD25, CD71) in serum of patients with chronic lymphocytic leukemia. 825 2


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