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)

Using the alkaline phosphatase-anti-alkaline phosphatase (APAAP) technique, plasma cells from multiple myeloma (MM, 23 cases), plasma cell leukemia (PCL, 2 cases) and reactive plasmacytosis (RP, 13 cases) were immunophenotyped with a panel of monoclonal antibodies (McAb). The results showed that McAbCD38 was strongly positive in high percentage of MM and RP cases and the CD9 was the next. 9/23 MM expressed CD10. Our results might indirectly support that CD10 is a malignant marker of MM with poor prognosis, a concept proposed by Durie. The results were (1) all RP but 1 acute monocytic leukemia related to RP were CD10 negative. (2) In our series 2 cases of plasma cell leukemia (PCL) expressed CD10; (3) 4 MM cases survived more than 2 years were CD10 negative. A few MM cases also expressed other surface markers of pre-B and B lymphocyte, such as CD19, CD20, CD22, HLA-DR, cytoplasmic mu chain. CD20 was positive in 4/21 MM and negative in all RP cases. 7/22 MM expressed HLA-DR, and 1/13 RP did so, among them there was a significant difference. HLA-DR seems to be another malignant marker of plasma cells. 1 MM expressed CD8, and 1 PCL highly expressed CD4 indicating PCL might be heterogeneous. Lymphoid stem cells may be involved in MM and PLC. We conclude that multiple myeloma cells have different immunophenotypes and CD10, CD20 and HLA-DR may help to differentiate MM from RP.
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PMID:[Preliminary study of immunophenotype of multiple myeloma cells]. 817 66

A review is given of the prognostic significance of immunophenotyping of blood lymphoplasmocytic cells. From a group of 250 patients followed from 1981 through 1991 a subgroup of 70 patients (followed 1986 through 1991) were phenotyped at 6-month intervals by immunofluorescence tests with monoclonal antibodies for cytoplasmic immunoglobulin, kappa-lambda index, CD71, CD10, CD20, CD38, and HLA-DR receptors. In course of a longitudinal study it was found that prognostic significance for shortened survival can be derived from the presence of circulating CD10, CD71, and CD20 positive undifferentiated cells in peripheral blood. There was a correlation between increase of CALLA positive and CD71 positive cells. Further, an increase of undifferentiated clone occurred during transition of the disease to an aggressive phase. The median survival of the total group of 250 patients treated by the VMCP/MOCCA protocol, according to statistical analysis, was 90 months, the median survival of the aggressive stage with plasmoblastic and lymphoplasmocytic cell type, respectively, was only 12 months. The significance of phenotypization in the prognostic evaluation of variant heterogenous myeloma types is stressed.
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PMID:Prognostic value of plasma-cell immunophenotype in patients with multiple myeloma. 828 66

The blood of multiple myeloma patients was examined for non-MHC-restricted cytotoxic lymphocytes. Four colour flow cytometry was used to phenotype the cells within a light scatter gate large enough to include all lymphocytes. NK and T cells were identified using CD16, CD56, and CD3 antibodies, and myeloid cells with CD13 and CD14 antibodies. Three subpopulations of NK cells and 3 subpopulations of CD16+ or CD56+ T cells were enumerated. The CD56+ NK and T cells were also examined with CD69, CD25, and anti-HLA-DR antibodies to assess their activation state. We found no evidence that either the percentage or the absolute number of any subpopulation of the NK cells or CD56+ T cells correlated with disease activity. Neither did we find any significant abnormalities in the numbers of activated CD56+ NK or T cells. We conclude that it is unlikely that circulating non-MHC-restricted cytotoxic lymphocytes are responsible for maintaining disease stability in myeloma patients with indolent disease.
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PMID:Natural killer cells and CD56+ T cells in the blood of multiple myeloma patients: analysis by 4-colour flow cytometry. 881 87

In this paper, the results of some recent studies on idiotype-specific T cells in human multiple myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS) are discussed. By using different in vitro measurements such as 3H-thymidine incorporation and ELI-SPOT assay, idiotype-specific T cells have been demonstrated in most of MM and MGUS patients. Based on the cytokine-secretion profiles, idiotype-specific T cells were found to comprise both Th1 and Th2 cells. A Th1 type immunity was found preferentially in indolent disease and a Th2-like response predominated in advanced MM, suggesting a specific T-cell regulation of the tumor B-cell clone. The mode of T-cell recognition of id determinants on M-components has been studied. We found that idiotype-specific T cells recognized processed id determinants presented by MHC class II (HLA-DR) molecules on APC. B cells were much more efficient APC than monocytes. With the aim to induce or to amplify an idiotype-specific T-cell response, we have immunized MM patients with the autologous M-component precipitated in aluminum. Three out of the five patients showed an induction of specific cellular and humoral immunity. Nevertheless, the role for such immunity in controlling the tumor clone remains to be established.
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PMID:Idiotype-specific T cells in multiple myeloma: targets for an immunotherapeutic intervention? 886 33

Peripheral blood stem cells (PBSC) are used increasingly for autotransplantation in the treatment of acute leukemia, lymphoma, multiple myeloma, solid tumors such as ovarian and breast carcinoma. They are collected by leukaphereses during rapid hematopoietic recovery, following cytotoxic chemotherapy with or without administration of hematopoietic growth factors. We studied the clonogenic and cytokine-mediated expansion potential of CD34+ cells from mobilized PBSC. Low density mononuclear cells were processed using the CEPRATE LC CD34 KIT (CellPro). CD34+ purified cells, were cultured in suspension with 6 combined hematopoietic growth factors (IL1beta, IL3, IL6 at 100 U/ml and G-CSF, GM-CSF and stem cell factor at 10 ng/ml of each) for up to four weeks. Every week, cells were counted and CFU-GM assay was performed in a methylcellulose based medium. We have analysed the percentage of cells bearing CD34, CD33, CD38, HLA-DR, CD45RA, CD45RO antigens. Our results showed, that CD34+ cells were obtained with a purity of 92 +/- 2.3% and a yield of 71 +/- 10.7%. The majority co-expressed CD33 (57.76 +/- 34.16%) and CD38 (62.2 +/- 34%) antigens. These culture conditions, are necessary to obtain a fold increase of nucleated cells (377 fold at week 4), of CFU-GM progenitors (41.2 fold at week 3) and of CD34+ cell absolute number (10 fold at week 1) with an important differentiation of progenitors in particular myeloid progenitors.
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PMID:Peripheral blood CD34+ cells: method of purification and ex vivo expansion. 890 32

Tumour-specific CD4+ T helper (Th) and CD8+ T cytotoxic (Tc) cells may participate in the control and eradication of tumour cells. In the present study, idiotype-specific stimulation of CD4+ and CD8+ blood T cells from patients with monoclonal gammopathy of undetermined significance and patients with untreated multiple myeloma stage I was examined. Activation was measured in the CD4+ and CD8+ subsets enriched by magnetic microbeads as the incorporation of 3H-thymidine and the secretion of interferon (IFN)-gamma, interleukin (IL)-2 and IL-4 by single cells using the enzyme-linked immunospot assay. Idiotype-specific T cells were found in four of seven patients. Stimulation was mainly confined to the CD4+ subset in three of the four responding patients. This type of response was major histocompatibility complex (MHC) class II restricted as it could be inhibited by monoclonal antibodies against MHC class II (HLA-DR), but not against class I (HLA-ABC) molecules. Idiotype-specific CD8+ T cells were also demonstrated in these patients although at a lower frequency. One patient showed a strong and dominating activation of CD8+ T cells which could be blocked by antibodies against HLA-ABC but not against HLA-DR. Idiotype-specific CD4+ or CD8+ T cells were mainly of the type-1 subsets as judged by their secretion of IFN-gamma and IL-2. Thus, this study provides evidence for the presence of idiotype-specific and MHC-restricted CD4+ and CD8+ T cells of the type-1 subsets in patients with monoclonal gammopathies. Such T cells with the potential to control the growth of tumour B cells may be a suitable target for immunotherapeutic interventions in patients.
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PMID:Idiotype-specific T lymphocytes in monoclonal gammopathies: evidence for the presence of CD4+ and CD8+ subsets. 902 23

Myeloma plasma cells constitute 10% to 90% of the total bone marrow cell count in patients with multiple myeloma (MM). These cells express a variety of cell surface markers, such as HLA-ABC and HLA-DR, and surface antigens that are necessary for professional antigen-presenting cells, including adhesion and costimulatory molecules. In this study, we examined the expression of major histocompatability complex (MHC) and costimulatory molecules on CD38(bright,++) plasma cells in bone marrow aspirates from eight MM patients. Small percentages of plasma cells expressed weak but detectable levels of HLA-DR, HLA-DQ, CD40, CD80, and CD86, which could be upregulated by interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha. CD38++ plasma cell and CD38(dim,+) cells were sorted from freshly isolated bone marrow mononuclear cells and tested for their capacity to act as antigen-presenting cells. Indeed, both CD38++ plasma cells and CD38+ cells were able to stimulate allogeneic T cells and present the soluble antigens purified protein derivative and tetanus toxoid to autologous T cells. Recognition of the antigens led to T-cell proliferation and secretion of IFN-gamma and was MHC class-I and -II restricted. Antigen processing and presentation by CD38++ and CD38+ cells were abolished by treatment of the cells with chloroquine. Hence, our study provides for the first time evidence that myeloma plasma cells may act as antigen-presenting cells. Further studies are warranted to examine in detail the molecules required for inducing T-cell stimulation.
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PMID:Myeloma bone marrow plasma cells: evidence for their capacity as antigen-presenting cells. 929 30

Using a combination of GM-CSF, SCF, flk-2/flt-3 ligand, and IL-4, dendritic cells (DC) have been generated in vitro from the adherent fraction of mononuclear cells isolated from the blood of patients with MM. Analysis of cell yield showed no significant difference in DC yield (numbers or percentage of leucocytes) or total number of leucocytes generated in myeloma cultures compared to similar cultures prepared using mononuclear cells from the blood of healthy donors. The mean number of DC produced after 10d of culture were 8.19 x 10(5) and 9.87 x 10(5) cells (41% and 51% of all leucocytes) for the myeloma and normal cultures respectively. Flow cytometry investigation of phenotypic markers including CD1a, HLA-DR, CD80 (BB1/B7.1) and CD86 (B70/B7.2), and functional status (stimulatory potential in allogeneic mixed leucocyte reactions (MLR)) confirmed the generation of cells phenotypically identified as cultured DC. In addition, these cells were more effective than PBMC at stimulating allogeneic PBMC proliferation. These data demonstrate no difference between DC generated from patients with MM and healthy donors. This study was considered a prerequisite for future investigations directed towards developing effective immunotherapies for myeloma.
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PMID:Dendritic cells generated from the blood of patients with multiple myeloma are phenotypically and functionally identical to those similarly produced from healthy donors. 932 98

Flow cytometry immunophenotyping of peripheral blood lymphocyte subsets and multivariate data-analytical techniques revealed that among untreated hemato-oncological patients (n = 48) with lymphomas, acute and chronic myeloid and lymphocytic leukemias, monoclonal gammopathy of undetermined significance, and multiple myeloma, 42% had (nonmalignant) lymphocyte profiles clearly distinct from healthy donors. Notably, a similar pattern of increased CD3+ CD57+, CD3+ HLA-DR+, CD3+ CD(16 + 56)+, CD4- CD8+, CD8+ CD57+, CD8+ CD28-, and CD8+ CD62L- subsets was detected. More extensive three-color immunophenotyping on an additional group of 49 untreated patients revealed that both CD4+ and CD8+ T cells displayed significant increases of activation markers: CD69, CD(16 + 56), HLA-DR, CD71, and CD57, and a loss of CD62L and CD28, which is also interpreted as a sign of activation. Consistent with the phenotypical signs of in vivo immune activation, polyclonal cytolytic activity, measured ex vivo in an anti-CD3-redirected assay, was detected within immunomagnetically purified CD4+ T cells of three out of six B-CLL patients investigated, but not within purified CD4+ T cells of five healthy donors. The purified CD8+ T cells of patients (n = 28) and donors (n = 5) on the other hand displayed similar polyclonal cytotoxic activities at the various effector:target ratios investigated. Tumor-directed cytotoxic activity of purified CD4+ (n = 6) and/or CD8+ T cells (n = 15) against freshly isolated autologous tumor cells was not detected in any of the experiments. Collectively, our results demonstrate systemic T cell activation as a common feature in hematological neoplasia, and a markedly enhanced cytolytic activity of the CD4- subset in CLL patients. The reason(s) for this expansion of activated T cells and its pathophysiologic significance, however, remain unclear.
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PMID:Peripheral blood lymphocyte subset shifts in patients with untreated hematological tumors: evidence for systemic activation of the T cell compartment. 959 74

With the exception of childhood common acute lymphoblastic leukaemia (cALL), treatment of other hematopoietic B cell lineage tumours such as non-Hodgkin's lymphoma (B-NHL), adult ALL and multiple myeloma (MM) is unsatisfactory. Similarly, the therapeutic outcome of acute and chronic myeloid leukaemia (AML, CML) is frequently dismal. At the same time, leukaemia/lymphoma cells represent ideal targets for immunotherapy. The present review summarizes our preclinical experience with a novel type of cytotoxic T cell based immunotherapy for B-lineage and myeloid tumours. Staphylococcal enterotoxin-derived superantigens (SAgs) are among the most potent T cell activators known, linking the T cell receptor to HLA-DR on natural target cells. SAgs were genetically engineered to reduce DR binding and were then fused to Fab parts of tumour-directed monoclonal antibodies (mAbs). Using these "targeted" SAgs, highly efficient lysis of B-lineage (B-NHL, B-CLL, ALL, MM) and myeloid (AML, CML) tumour cells by T-cells was achieved in vitro and in an animal model. We are entering an interesting era of innovative cancer therapy based on novel man-made biotherapeutic agents.
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PMID:Targeted superantigens for immunotherapy of haematopoietic tumours. 970 86


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