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)

Hybridoma cell lines secreting monoclonal antibodies that bind to a surface antigen of human neutrophils have been prepared by fusion of mouse myeloma cells with spleen cells from mice immunized with human neutrophils. Several of the monoclonal antibodies (AHN 1-6) were specific for a neutrophil surface antigen and did not bind lymphocytes, monocytes, red blood cells, platelets, or basophils. All of the granulocyte-specific antibodies immunoprecipitated a polypeptide of 145,000 daltons and an isoelectric point of about 4.5 and other heterogeneous polypeptides of 105,000 daltons. These same components were the major lactoperoxidase-labeled proteins precipitated by hyperimmune mouse serum. The antibodies were further characterized for binding to several human myeloid leukemia cell lines and cells from patients with myeloid or lymphoid leukemia. All antibodies bound the HL-60, ML1, ML2, ML3, K562, and U937 myeloid leukemia cell lines. None of the antibodies bound the RPMI 6410 Raji, RPMI 8226, MOLT 4, or Daudi lymphoid cell lines. All of the hybridoma cell lines (AHN 1-6) produced IgM antibodies that were cytotoxic.
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PMID:A human granulocyte-specific antigen characterized by use of monoclonal antibodies. 684 44

In a 66-year old man without previous major disease the unexpected finding of pancytopenia on routine blood count during an acute respiratory infection led to the diagnosis of IgG-producing myeloma without radiological bone lesions, associated with partial blastocytosis and abnormalities in granulocyte maturation. No treatment was given. Within 15 days, the circulating blastocytes became more numerous and type M1 acute myeloblastic leukaemia was diagnosed. A combined rubidazone and cytosine arabinoside treatment failed, and the patient died rapidly.
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PMID:[Myeloma together with acute myeloblastic leukaemia in an untreated patient (author's transl)]. 693 6

An autoantibody that reacted with nuclei of polymorphonuclear neutrophils (PMN) was detected at titers of greater than 10 in sera of 25 of 50 patients with rheumatoid arthritis and 36 of 50 with autoimmune chronic active hepatitis but in none of 160 controls comprising 24 patients with alcoholic cirrhosis, 36 with multiple myeloma, and 100 healthy subjects. Through the use of enriched populations of hemopoietic cells, this antibody was shown to be cell-specific, reacting only with the nucleus of the mature neutrophil. It was unreactive with nuclei of progenitor cells in the myeloid series and with nuclei of eosinophils, monocytes, lymphocytes, and thymocytes. It reacted with a determinant that appeared to be a differentiation antigen. This cell-specific autoantibody may prove to be of value in analytical studies of granulocyte maturation.
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PMID:An autoantibody reactive with nuclei of polymorphonuclear neutrophils: a cell differentiation marker. 702 71

This chapter outlines our development of an in vitro soft agar assay for detection of human myeloma colony-forming cells. Growth was induced with either 0.02 ml of human type O erythrocytes or 0.25 ml of medium conditioned by the adherent spleen cells of mineral-oil-primed BALB/c mice. A maximum plating efficiency of 0.1% was obtained. The number of myeloma colonies was proportional to the number of cells plated between concentrations of 105--106/ml. Morphological, histochemical, and functional criteria showed the colonies to consist of immature plasmablasts and mature plasma cells. 60%--80% of cells picked from colonies contained intracytoplasmic monoclonal immunoglobulin. Tritiated thymidine suicide studies provided evidence that for most myeloma patients, a very high proportion of myeloma colony-forming cells were actively in transit through the cell cycle. Using biophysical and immunologic studies, we were able to further characterize myeloma stem cells and obtain partial enrichment of the colony-forming cells. Increased numbers of myeloma colonies were seen when the marrow was depleted of CSF, elaborating adherent cells before plating. Antibody to granulocyte colony-stimulating factor, which did inhibit granulocyte colony formation, did not reduce the number or size of the myeloma colonies. This bioassay has subsequently served as the basis for studies of in vitro biological behavior of multiple myeloma, and for measurement of drug sensitivity. The general methodology which we first developed for myeloma appears to have general applicability not only to monoclonal plasma cell disorders, but also to many other tumor types as well. Detailed biological studies and analysis of culture conditions (similar to those we have carried out in myeloma) will no doubt prove important in understanding the biology and drug sensitivity of various forms of human cancer.
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PMID:Development of a bioassay for human myeloma colony-forming cells. 720 18

In the present study the gene expression of cytokines promoting in vitro myeloma-cell growth was investigated by Northern blot analysis using total RNA of 36 tumour samples of patients with multiple myeloma (MM) or plasma cell leukaemia and poly(A)+ RNA of 10 human myeloma cell lines (HMCL). These cytokines included interleukin (IL)-1 alpha, IL-1 beta, IL-3, IL-6, granulocyte-macrophage (GM)-colony-stimulating factor (CSF) and granulocyte (G)-CSF. IL-1 beta, IL-6 and G-CSF genes were coexpressed in most patients, although at variable levels. IL-1 alpha transcripts were detected in 32% of patients in whom coexpression of IL-1 beta gene was found. IL-3 gene was not expressed in patients' cells and GM-CSF mRNA was detected in only 1/32 patients. No detectable transcripts for the above cytokines were present in HMCL, whereas IL-6 gene was expressed in 2/10 HMCL. We also looked for the presence of transcripts for IL-2, leukaemia inhibitory factor (LIF) and transforming growth factor (TGF)beta in cells of tumour samples from the same patients and in HMCL. IL-2 gene was not expressed in MM patients and HMCL. Weak expression of LIF gene was detected in three patients (9%), and transforming growth factor beta (TGF beta) mRNA was observed in 12/12 tumour samples analysed and all HMCL. These results suggest that, among cytokines shown to control myeloma-cell growth in vitro, IL-1, IL-6 and G-CSF could play a role in the development of myeloma disease in vivo.
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PMID:Cytokine gene expression in human multiple myeloma. 751 Sep 89

A panel of 164 continuous human leukemia-lymphoma cell lines was analyzed for expression of c-kit using Northern blotting and reverse transcriptase-polymerase chain reaction (RT-PCR). The c-kit transcripts were detectable in cell lines assigned to the myeloid (in 7 of 29 by Northern blotting and in 4 of 8 by RT-PCR), monocytic (in 1 of 24 by Northern blotting and in 3 of 6 by RT-PCR), erythroid (in 6 of 8 by Northern blotting and in 5 of 5 by RT-PCR), and megakaryoblastic (in 10 of 10 by Northern blotting) lineages, c-kit expression was not seen by Northern blotting or RT-PCR analysis in any of the 93 lymphoid leukemia, myeloma, or lymphoma cell lines. Treatment of four megakaryoblastic cell lines with protein kinase C activators (phorbol ester 12-O-tetradecanoylphorbol 13-acetate and Bryostatin 1) led to terminal differentiation as assessed by morphologic alterations, changes in the surface marker profile, and growth arrest. These effects were associated with enhanced c-kit mRNA expression. Exposure to all-trans retinoic acid down-regulated c-kit mRNA levels, while simultaneously causing morphologic alterations in all four cell lines. Stimulation with growth factors (interleukin-3, granulocyte macrophage-colony stimulating factor, and insulin-like growth factors I and II), used to assess any role of c-kit in proliferative processes, did not lead to significant upregulation or downregulation of c-kit expression. The finding of constitutive and high expression of c-kit mRNA in all megakaryoblastic leukemia cell lines and its modulation by various reagents might further contribute to the understanding of megakaryopoietic proliferation, differentiation, and leukemogenesis.
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PMID:c-kit expression in human megakaryoblastic leukemia cell lines. 751 41

In contrast to its clearly defined role as a multidrug efflux pump in neoplastic cells, the physiologic function of P-glycoprotein (P-gly) in normal cells is unclear. Recent reports identifying P-gly in normal blood and bone marrow suggest that hematopoietic development or function may be dependent on P-gly. To understand the normal function of P-gly in the blood, its level of expression and function must first be quantitated relative to a known standard. In this study, P-gly, MDR1 gene expression, and P-gly function were quantitated in normal leukocytes. P-gly and MDR1 expression were analyzed in individual leukocyte lineages (T-helper, T-suppressor, monocyte, granulocyte, B-lymphocyte, NK cell) from normal volunteers. P-gly on the cell surface was detected by fluorescent double-labeling for lineage (CD4, CD8, CD14, CD15, CD19, CD56, respectively) and P-gly (MRK16) with analysis by flow cytometry and in some cases immunoblot analysis. MDR1 mRNA analysis on purified lineages was performed using quantitative reverse transcription-polymerase chain reaction. P-gly function was determined for each lineage using dual-labeling for lineage and P-gly substrate (rhodamine 123). The P-gly expressing human myeloma cell line, 8226/Dox6, was used as a reference of comparison for levels of P-gly, MDR1 mRNA, and function. CD56+ cells expressed the highest levels of MDR1 mRNA followed by CD8+ > CD4+ approximately equal to CD15+ > CD19+ > CD14+, with percentage values relative to Dox6 of 49%, 17%, 8%, 8%, 4%, and 2%, respectively. The assays for P-gly immunofluorescence and function correlated well with mRNA analysis except for CD15+ cells (granulocytes), which showed a moderate MDR1 mRNA level with a lack of both function and surface P-gly staining. Granulocyte membranes did show P-gly on immunoblot analysis when probed with either C219 or JSB1. We conclude that (1) P-gly and the MDR1 mRNA are expressed in normal leukocytes, (2) this P-gly expression is lineage specific with relatively high levels among CD56+ cells, and (3) the expression of P-gly in granulocytes is not associated with transport of the P-gly substrate, rhodamine 123, out of the cell.
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PMID:P-glycoprotein expression and function in circulating blood cells from normal volunteers. 751 98

We report the development of a potent anti-CD38 immunotoxin capable of killing human myeloma and lymphoma cell lines. The immunotoxin is composed of an anti-CD38 antibody HB7 conjugated to a chemically modified ricin molecule wherein the binding sites of the B chain have been blocked by covalent attachment of affinity ligands (blocked ricin). Conjugation of blocked ricin to the HB7 antibody has minimal effect on the apparent affinity of the antibody and no effect on the ribosome-inactivating activity of the ricin A-chain moiety. Four to six logs of CD38+ tumor cell line kill was achieved at concentrations of HB7-blocked ricin in the range of 0.1 to 3 nmol/L. Low level of toxicity for normal bone marrow (BM) granulocyte-macrophage colony-forming units (CFU-GM), burst-forming units-erythroid (BFU-E), colony-forming units-granulocyte/erythroid/monocyte/macrophage (CFU-GEMM) cells was observed. Greater than two logs of CD38+ multiple myeloma cells were depleted from a 10-fold excess of normal BM mononuclear cells (BMMCs) after an exposure to HB7-blocked ricin under conditions (0.3 nmol/L) that were not very toxic for the normal BM precursors. HB7-blocked ricin was tested for its ability to inhibit protein synthesis in fresh patients' multiple myeloma cells and in normal BMMCs isolated from two healthy volunteers; tumor cells from four of five patients were 100-fold to 500-fold more sensitive to the inhibitory effect of HB7-blocked ricin than the normal BM cells. HB7 antibody does not activate normal resting peripheral blood lymphocytes, and HB7-blocked ricin is not cytotoxic toward these cells at concentrations of up to 1 nmol/L. The potent killing of antigen-bearing tumor cells coupled with a lack of effects on peripheral blood T cells or on hematopoietic progenitor cells suggests that HB7-blocked ricin may have clinical utility for the in vivo or in vitro purging of human multiple myeloma cells.
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PMID:Anti-CD38-blocked ricin: an immunotoxin for the treatment of multiple myeloma. 771 3

In order to assess the contamination with malignant cells of peripheral blood stem cell (PBSC) transplants used to support high-dose therapy in multiple myeloma (MM), we used the immunoglobulin heavy chain gene radioactive fingerprinting polymerase chain reaction (PCR) method to detect clonal cells in PBSC from 10 patients. The sensitivity of the technique allowed the detection of one clonal cell among 10(4) normal blood mononuclear cells. A clonal band was detected in 4 of 11 leukaphereses samples. The level of contamination was low because a clonal band could never be identified on ethidium bromide-stained agarose gels whose sensitivity is between 1 and 5%. The use of granulocyte-colony stimulatory factor (G-CSF) in combination with chemotherapy in three cases did not seem to increase the contamination of PBSC grafts; in one patient, G-CSF was used during a second course of leukapheresis which was free of detectable clonal cells whereas the first one performed after chemotherapy alone contained clonal cells. Thus, PBSC grafts may rarely be completely devoid of clonal potentially malignant cells but the level of contamination is much lower than in BM grafts. Whether graft contamination is an important adverse prognostic factor for patients with MM undergoing intensive treatment and autografting is still unsettled.
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PMID:Myeloma cell contamination of peripheral blood stem cell grafts in patients with multiple myeloma treated by high-dose therapy. 752 6

We have investigated the properties of mobilized, cryopreserved, peripheral blood stem cells (PBSC), collected by leukapheresis over a period of 5 days, from eight myeloma patients in clinical remission. Cells were mobilized by treatment with cyclophosphamide and granulocyte colony-stimulating factor (G-CSF), and each day's collection was evaluated for its content of CD34+ cells, colony-forming units granulocyte/macrophage (CFU-GM), and plastic-adherent pre-CFU-GM. Peak values for these three parameters were observed at different times in different patients. There was no correlation between CD34+ content and CFU-GM, but there was some (r = 0.65) between CD34 numbers and colonies generated from a delta assay initiated using plastic-adherent pre-CFU-GM. In suspension cultures, the cells grew exponentially for 50 days. Thereafter, they did not divide, although they remained viable in culture for up to 1 month longer. Suspension cultures of PBSC grown with interleukin-3 (IL-3) displayed a predominantly myelomonocytic phenotype, but some megakaryocytes and erythroid cells were observed consistently. These results indicate that pre-CFU-GM in PBSC collections are capable of generating large numbers of clonogenic progeny in liquid culture and are capable of producing multiple lineages of differentiation.
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PMID:In vitro proliferation by cells mobilized into the peripheral blood for collection and autologous transplantation. 752 29


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