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)

To further characterize the B-cell origin of multiple myeloma, our laboratory performed immunoglobulin gene sequence analyses of four cases of myeloma (three immunoglobulin A and one immunoglobulin G). Three tumors expressed VH3 genes and one expressed a VH1 gene, while the light chains included two V lambda and one V kappa III; one light chain was not isolated. The closest homology to published germ line genes ranged from 91 to 97%. In two cases, the expressed VH genes were compared with the putative germ line precursor VH genes isolated from autologous granulocyte DNA and appeared to have mutated randomly from the germ line gene. By sequencing multiple clonal isolates from each tumor sample, we found no evidence for ongoing mutation in three cases; in one case, however, clonotypic heterogeneity was evident. The analysis of DH- and JH-region genes revealed (i) limited or absent N nucleotide insertions (two of four cases), (ii) the presence of a DH-JH junction resulting from sequence overlap between the DH and JH genes (one of four cases), (iii) the absence of somatic mutations (two of four cases), and (iv) restricted JH gene usage of a JH6 polymorphism (three of four cases). These analyses of DH and JH genes suggest that multiple myeloma, similar to what has been proposed for chronic lymphocytic leukemia, may derive from B cells which have rearranged during fetal development rather than during adult life.
 ...
PMID:Immunoglobulin gene sequence analysis to further assess B-cell origin of multiple myeloma. 771 12

The association of plasma cell myeloma and eosinophilia is rare. The authors describe a 49-year-old man with plasma cell myeloma and marked absolute peripheral blood eosinophilia, 109.7 x 10(9)/L. Analysis of his bone marrow revealed cytologically atypical plasma cells that expressed monotypic IgG lambda and marked eosinophilia with normal maturation. A combination of steroids and chemotherapy resulted in a significant and sustained decrease in his absolute eosinophil count and bone marrow plasma cells. Analysis of the patient's pre-therapy serum revealed immunoreactive interleukin-3 (IL-3), but not IL-5 or granulocyte/macrophage colony stimulating factor (GM-CSF). The post-therapy serum sample was negative. Immunohistochemical analysis of the plasma cells for IL-3 and IL-5 was negative. This review of the literature has revealed five cases of plasma cell myeloma associated with eosinophilia described previously. In two patients, the eosinophilia was attributed to drug therapy. In the remaining cases, the pathogenesis of the eosinophilia was unexplained. In this case, IL-3 secreted either by the neoplastic cells at a level below detection by immunohistochemistry or by other cells in response to the presence of plasma cell myeloma may have played a role in causing the eosinophilia.
 ...
PMID:Plasma cell myeloma associated with eosinophilia. 774 Nov 3

A retrospective study was undertaken to assess the factors affecting the yield of peripheral blood stem cell (PBSC) collections after chemotherapy. Fifty-five patients with malignancies, observed in 4 Italian Institutions from January 1987 to June 1991 were eligible for evaluation. This series included 19 non-Hodgkin lymphoma, 11 multiple myeloma, 9 ovarian cancer, 7 Hodgkin disease, 7 acute non-lymphocytic leukemia, 1 acute lymphoblastic leukemia, 1 neuroblastoma. Five hundred and twenty two PBSC collections were performed on 55 patients after a median of 18 days after the start of chemotherapy. The yields of PBSC collections were related to the dose of cytoreductive chemotherapy exploited for PBSC mobilization and to the number of circulating white blood cells, colony forming unit granulocyte/macrophage (CFU-GM) and the percentage of monocytes at the time of collection. Forty-eight patients out of 55 transplanted (87%) had rapid, complete and sustained engraftment. Three patients (5%) died of transplant related complications.
 ...
PMID:Autologous blood stem cell collection after chemotherapy in patients with sensitive and refractory malignancies: a multicenter retrospective study. 791 30

We have previously reported that polymorphonuclear granulocyte (PMN) and monocyte oxidative metabolism is reduced in polycythemia vera (PV) patients compared to healthy control subjects, after stimulation with cell surface receptor-dependent stimuli such as n-formyl-methionyl-leucyl-phenylalanine, leukotriene B4 and platelet-activating factor (PAF). In contrast, the oxidative response to phorbol myristate acetate (PMA) is normal. We now show that, in PV patients exhibiting significantly reduced PMN chemiluminescence after PAF stimulation, PAF induced platelet aggregation was also reduced--40 +/- 3% compared to 50 +/- 2% in controls (p < 0.01). The defective aggregatory response to PAF in PV remained over a wide range of stimuli concentrations. Platelet aggregation induced by PMA and ADP, however, was similar in PV and controls. In contrast, platelet aggregation induced by PAF (or by ADP and PMA) was not significantly reduced in patients with chronic myeloid leukemia, essential thrombocythemia and multiple myeloma. Furthermore, the release of beta-thromboglobulin was slightly but not significantly higher after PAF stimulation in PV and this argues against an abnormal PAF receptor as the cause of the defective function. Thus, not only PV neutrophils, but also PV platelets show a discrete defect of the stimulus response coupling for PAF, indicating a disease-specific abnormality that appears to be of clonal origin.
 ...
PMID:Stimulus-specific defect in platelet aggregation in polycythemia vera. 792 57

Follicular dendritic cells (FDC) are specialized cells residing primarily within lymphoid follicles. They bind immunocomplexes and play an important role in the presentation of antigen to follicular B cells. Isolation of FDC for in vitro studies, however, is difficult because they constitute only about 1% of the cells in lymphoid tissue and form tight clusters entrapping lymphocytes within their dendritic processes. The monoclonal antibody (mAb) Ki-M4, which is highly restricted in its binding to FDC, is used to identify these cells. In order to establish a new immortalized cell line with features of FDC, we applied a modified procedure to isolate and enrich FDC from human tonsils and fused them with the myeloma cell line SP2/0-Ag14. The new hybrid cell line, designated FDC-H1, is of both mouse lymphoid and human FDC origin. FDC-H1 was found to have unlimited growth potential and to consistently express the Ki-M4 antigen and other surface antigens of human FDC. Semiquantitative reverse-transcribed polymerase chain reaction (RT-PCR) of enriched FDC and FDC-H1 revealed the same highly restricted cytokine/mRNA profile for both, with detectable levels of interleukin (IL)-1 alpha and surface CD23 and a lack of mRNA for IL-1 beta, IL-2, IL-3, IL-4, IL-7, IL-9, IL-10, interferon-gamma, tumor necrosis factor-alpha, transforming growth factor-beta and granulocyte/macrophage-colony-stimulating factor. Additionally a weak but constant IL-6 mRNA expression was found in the cell line FDC-H1 by RT-PCR. In situ hybridization experiments in tonsils revealed IL-6 transcripts in cells with a staining pattern characteristic of a dendritic cell only in a few germinal centers. To our knowledge, FDC-H1 is the first cell line that constantly expresses surface antigens and a cytokine profile characteristic of FDC. It is, therefore, well suited for studying the biology of FDC and the functional relationship between FDC and normal or neoplastic lymphatic cells.
 ...
PMID:An immortalized cell line with features of human follicular dendritic cells. Antigen and cytokine expression analysis. 795 61

Peripheral blood stem cells (PBSC) from 15 patients with advanced non-Hodgkin's lymphoma (NHL), two patients with chronic lymphocytic leukemia, and two patients with myeloma were collected by continuous-flow leukapheresis after chemotherapy with MIV (mitoxantrone, ifosfamide, and etoposide, five patients) or high-dose cyclophosphamide (14 patients), followed by administration of GM-CSF. Sixteen patients (84%) had persistent marrow involvement at time of inclusion. Results were compared to those obtained in a control group of similar age and disease status in whom collection had been performed after MIV chemotherapy alone. The number of mononuclear cells, granulocyte-macrophage colony-forming units (CFU-GM), CD34+ cells were higher in GM-CSF treated patients with a lower mean number of leukapheresis (3.5 versus 6.4). Among the 19 patients harvested after chemotherapy plus GM-CSF, more progenitor cells were obtained in the cyclophosphamide group than in the MIV group. In all these patients except one, the number of mononuclear cells was sufficient to realize a transplantation. Seventeen patients received intensification with BEAM regimen (8 patients) or cyclophosphamide plus etoposide and total body irradiation (9 patients). Two patients failed to reconstitute correct hematopoiesis and three early toxic deaths occurred for a total of five procedure-related deaths. Nine of these 17 patients are in persistent complete remission with a median post-transplant follow-up of 18 months. Time to reach granulocyte and platelet recovery was not correlated with the number of mononuclear cells, CFU-GM, granulocyte-erythroid-macrophage-megakaryocyte colony-forming units (CFU-GEMM), CD34+ cells, and CD34+ CD33- cells but with the number of previous chemotherapy regimens. PBSC harvesting is achievable after chemotherapy plus GM-CSF in heavily pretreated patients with persistent marrow involvement. Moreover, these cells are able to reconstitute correct hematopoiesis after intensive treatment in these patients.
 ...
PMID:Peripheral blood stem cells harvested after chemotherapy and GM-CSF for treatment intensification in patients with advanced lymphoproliferative diseases. 810 11

Forty patients with multiple myeloma received thiotepa (750 mg/m2), busulfan (10 mg/kg), and cyclophosphamide (120 mg/kg) (TBC) followed by autologous bone marrow or blood stem cell support. Granulocyte-Colony stimulating factor (G-CSF) was administered to accelerate hematopoietic recovery. Sixty-five percent of all patients responded to this treatment. Eighty-eight percent of patients transplanted in partial remission had a further reduction of the myeloma and 53% achieved a complete remission. Forty-eight percent of patients with refractory myeloma responded. All responding patients transplanted during partial remission or with primary refractory myeloma remain free of progression for a period of 4 to 24 months post-transplant, but the remission duration of patients treated in refractory relapse was short (4 months). Five of 24 patients transplanted with marrow and none of 16 receiving blood stem cells died of treatment-related complications. Use of blood stem cells resulted in more rapid granulocyte and platelet recovery. We conclude that TBC is an effective, relatively well tolerated, preparative regimen for patients with multiple myeloma.
 ...
PMID:Thiotepa, busulfan, and cyclophosphamide: a new preparative regimen for autologous marrow or blood stem cell transplantation in high-risk multiple myeloma. 810 39

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.
 ...
PMID:Reproducible obtaining of human myeloma cell lines as a model for tumor stem cell study in human multiple myeloma. 820 90

The cytotoxicity of a recombinant interleukin 6 (IL-6)-diphtheria toxin (DT) fusion protein towards human myeloma cell lines was investigated. DAB389-IL-6 inhibited protein synthesis and methylcellulose colony formation by U266 myeloma cells. In the clonogenic assay, the fusion protein approached the level of cytotoxicity achieved by native DT. The specificity of killing by DAB389-IL-6 was demonstrated by inhibition of cytotoxicity by a molar excess of free rhIL-6. The effect of DAB389-IL-6 on colony formation by six OCI-My cell lines was assessed. Similar to U266 cells, colony growth by the OCI-My 5 and -My 2 cell lines was inhibited in a simple dose dependent manner. However, a biphasic effect was observed for the IL-6 dependent OCI-My 4 cells; DAB389-IL-6 stimulated colony formation at low (< or = 10(-11) M) concentrations, yet was inhibitory at higher doses. Three other cell lines whose growth was not altered by IL-6 were relatively unaffected by DAB389-IL-6, despite their sensitivity to native DT. Flow cytometric analysis for IL-6 receptor expression using phycoerythrin-conjugated IL-6 demonstrated specific binding sites on both DAB389-IL-6 sensitive and certain insensitive cell lines, suggesting that other factors in addition to the expression of IL-6 receptors are involved in killing by the fusion toxin. Despite evidence for a role of IL-6 in myeloid cell development, normal bone marrow was insensitive to the IL-6 fusion toxin. In cultures containing both normal bone marrow and U266 cells DAB389-IL-6 effectively inhibited the growth of U266 myeloma colonies but had little effect on normal bone marrow erythroid, granulocyte and mixed erythroid/granulocyte colony growth. From these experiments we conclude that DAB389-IL-6 is specifically cytotoxic towards a subset of IL-6-responsive human myeloma cell lines and may be useful, in some cases, in the selective elimination of tumour cells from mixed populations of normal and malignant cells.
 ...
PMID:Differential sensitivity of human myeloma cell lines and normal bone marrow colony forming cells to a recombinant diphtheria toxin-interleukin 6 fusion protein. 825 7

In an attempt to offset the impaired hematopoietic progenitors' mobilization and collection which are frequently encountered in multiple myeloma (MM), we have started a pilot study to evaluate the ability of a combination of high-dose melphalan (HDM) and sequential s.c. administration of recombinant human interleukin 3 (rhIL-3) and rh-granulocyte colony-stimulating factor (G-CSF) to mobilize blood cells (BC) in MM patients. Two different schedules for administration were successively tested. Schedule A consisted of IL-3 (5 micrograms/kg/d) from day 7 to day 11 after HDM followed by G-CSF (5 micrograms/kg/d) from day 12 to day 20. Under schedule B, HDM was followed by IL-3 alone at the same dosage from day 1 to day 3, IL-3 and G-CSF (idem) from day 4 to day 7 and G-CSF alone from day 8 until completion of apheresis. Two patients (one previously untreated, one having received prior chemotherapy for one year) underwent schedule A; three patients (one previously untreated, two pretreated) underwent schedule B. The post-HDM aplasia was not shortened in schedule A patients in comparison to what we usually observed following HDM alone (25 days) correlated with a very moderate two- to three-fold CD34+ cell increase. Only one patient was further transplanted with apheresis products: the post-transplant granulocyte recovery was slower than usual (16 days versus 12 days) while platelet count never recovered over 20 x 10(9)/l. In contrast, the post-HDM aplasia was significantly shortened in two of the schedule B patients (3 to 10 days) and was followed by a 25- to 165-fold increase in CD34+ cells.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Mobilization of peripheral blood stem cells with chemotherapy and cytokines in multiple myeloma. 852 May 4


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>