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Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Despite their generally favorable mortality experience, general occupational surveys of farmers suggest they have elevated risks of cancer of the lymphatic and hematopoietic systems, stomach, prostate, brain, and skin. Since farmers often serve in the role of mechanic, carpenter, welder, pesticide applicator, and veterinarian, they may be exposed to many potentially hazardous substances. The types and levels of exposures have been discussed by others earlier in the program. The evidence is strongest for the association between farming and risk of leukemia. However, the specific leukemogenic agent or agents have yet to be identified. Leukemia excesses among poultrymen and dairy farmers suggest involvement of zoonotic viruses, while associations with crop production is more indicative of pesticide usage. The associations regarding other cancers (i.e., Hodgkin's disease, non-Hodgkin's lymphoma, multiple myeloma, soft-tissue sarcoma, and cancers of the stomach, brain, and prostate) are even less clear. However, the Swedish reports of high risk of soft-tissue sarcomas and lymphomas among persons exposed to herbicides is particularly disconcerting and underscores the urgent need for similar epidemiologic studies in the U.S. Several case-control interview studies are underway that should help clarify the role of agricultural factors in the origin of various cancers. NCI is sponsoring studies of leukemia and non-Hodgkin's lymphoma among men from Minnesota and Iowa. Detailed information on farm practices and pesticide usage is being gathered. A study of soft-tissue sarcoma, Hodgkin's disease, and non-hodgkin's lymphoma also has just been initiated. This investigation is located in Kansas, a major wheat producing area. A wheat producing area was selected because herbicides are more heavily used on this crop than insecticides. The major objective of this project is to evaluate the role of herbicides in the origin of these cancers. A case-control study of brain cancer has also recently been initiated. Although this study focuses on contact with petrochemicals, a complete work history will be obtained and would note any farm experience. These data may help clarify the reported association between brain cancer and farming.
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PMID:Cancer risks associated with agriculture: epidemiologic evidence. 715 Feb 8

Immunophenotypic studies show the presence of CD10-bearing malignant cells in a small subset of multiple myeloma (MM) patients. We used a sensitive PCR-based technique in order to determine the frequency that MM patients contain a malignant subpopulation which expresses this antigen. The immunoglobulin (Ig) heavy chain variable region (VH) gene sequence expressed by the malignant clone in MM can be used as a tumor specific marker. After determining this sequence in six MM patients, patient specific VH oligonucleotide primers from complementarity determining region (CDR) sequences were generated. Bone marrow mononuclear cells from these patients were incubated with two different anti-CD10 antibodies or isotype identical murine IgG controls. Cells were then sorted by flow cytometry into the 1% brightest cells containing > 99.99% CD10-positive cells and two fractions including the 90 and 10% dimmest staining cells. PCR amplification was performed on DNA from approximately 10(4) cells (0.1 microgram) using patient specific CDR1 and CDR3 primers. Detectable PCR product was obtained in each sorted sample although the intensity of the band was much higher in cells lacking CD10 expression (the 90 and 10% dimmest fractions) than in the CD10-bearing (1% brightest) population. These results imply that there is a small population of CD10-bearing clonal cells in most, if not all patients with MM.
Leukemia 1995 Nov
PMID:A CD10-positive subset of malignant cells is identified in multiple myeloma using PCR with patient-specific immunoglobulin gene primers. 747 88

Gene-therapy of blood-borne disorders may be best achieved using hematopoietic stem cells (HSC) which have extensive self renewal potential as well as multilineage repopulating potential as a cellular target. The human HSC, which is CD34+Thy-1+Lin- has been isolated from fetal, adult bone marrow and cytokine-mobilized peripheral blood (MPB) (1-3). Results presented in this study show that the degree of mobilization of HSC into peripheral blood of cancer patients is highly variable and that the combined use of high dose chemotherapy and GM-CSF as a mobilization strategy is superior to the use of G-CSF with regard to the mobilization of true HSC. A multistep cell isolation procedure has been developed which utilizes high speed flow-cytometric cell sorting and allows the isolation of sufficient numbers of HSC from MPB to permit their use as an hematopoietic graft for clinical transplantation. Hematopoietic stem cells isolated from MPB are capable of self-renewal and differentiation into multiple hematopoietic lineages as shown by their behavior in both in vitro and in vivo assays. Mobilized PB mononuclear cells isolated from cancer patients are frequently contaminated with tumor cells. Using this cell isolation procedure, HSC preparations from patients with multiple myeloma have been created with greatly reduced tumor cell burdens. These CD34+Thy-1+Lin- cells are capable of being stably transduced at high efficiency (32-75%) by co-culture on a cell line producing recombinant retroviruses containing the neomycin-resistant gene. These HSC cell populations are likely ideal targets for hematopoietic cell-based gene therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
Leukemia 1995 Oct
PMID:Cytokine-mobilized peripheral blood CD34+Thy-1+Lin- human hematopoietic stem cells as target cells for transplantation-based gene therapy. 747 7

The change in phenotype, number and proliferative capacity of peripheral blood hematopoietic progenitors (PBHP) was studied in six patients with multiple myeloma during hematopoietic recovery after mobilization with high-dose cyclophosphamide and GM-CSF or G-CSF. In all six patients the first CD34+ cells appearing in the peripheral blood (PB) after cytoreductive treatment were predominantly CD34+/33- (> 70%). At later stages when leukapheresis procedures were started, the CD34+/33+ cells predominated in five of six patients. In leukapheresis harvests of peripheral blood, and in bone marrow addition of SCF and IL-6 to the culturing medium enhanced the plating efficiency. In peripheral blood an increase from 12 to 22% for CD34+/33+ and from 6 to 14% for CD34+/33- was observed. In normal bone marrow we observed an increase from 15 to 23% for CD34+/33+ and from 7 to 17% for CD34+/33-. Highly proliferative progenitors (>500 cells) in the CD34+/33- fraction appeared to be dependent on the addition of 'stem cell recruiting factors' (SCF and IL-6); in bone marrow the percentage of wells with >500 cells increased from 0.9 to 12.6% after SCF+IL-6 and in PBHP from 2 to 9%. We conclude that the first progenitors appearing in the peripheral blood after priming with high-dose cyclophosphamide and GM- or G-CSF have a more primitive immunophenotype, CD34+/33-.
Leukemia 1994 Dec
PMID:Primitive multilineage progenitor cells predominate in peripheral blood early after mobilization with high-dose cyclophosphamide and GM-CSF or G-CSF. 752 61

A new human monoclonal plasma cell line, designated UTMC-2, was established from the pleural effusion of a patient with immunoglobulin (Ig)A kappa-related multiple myeloma. The cultured cells were Epstein-Barr virus-negative and exhibited the morphological and ultrastructural features characteristic of plasma cells. Immunohistochemical analyses revealed the presence of cytoplasmic IgA kappa as well as the plasma cell-associated surface antigens CD38 and CD56. Other B-cell markers, including CD10, CD19, CD20, and HLA-DR, were absent. The UTMC-2 cells were interleukin (IL)-6 responsive: Co-culture with IL-6 increased IgA kappa synthesis and cell proliferation in a dose-dependent manner. In contrast, an IL-6 antisense oligonucleotide had an opposite effect. Although the UTMC-2 cells expressed IL-6 mRNA (as demonstrated by reverse transcriptase-polymerase chain reaction (RT-PCR)) and contained IL-6, the concentration of this cytokine in cell culture supernatants was less than that detectable by the enzyme-linked immunosorbent assay (ELISA) employed (i.e. <3 pg/ml). Further, cell growth was not inhibited by polyclonal or monoclonal anti-IL-6 antibodies. Flow cytometric analysis revealed that IL-6 receptors present on the surface of the UTMC-2 cells were not saturated with endogenous IL-6. Taken together, these results indicate that, in this human plasma cell line, IL-6 functions uniquely in an intracellular autocrine fashion to enhance Ig synthesis and cell growth. In this respect, the UTMC-2 cells represent a novel resource for further study of the role of IL-6 in the pathogenesis of multiple myeloma.
Leukemia 1994 Dec
PMID:Characterization of a novel interleukin-6 autocrine-dependent human plasma cell line. 752 62

PCR amplification of IgH gene V-D-J junctional variability (IgH PCR) is increasingly replacing Southern analysis for the detection of clonal lymphoid populations in cases presenting diagnostic difficulties. In order to determine the most efficient strategy, we have compared three known methods, using consensus primers against the VH FR3 or FR2 (FR256) regions, or a mix of six primers against the FR1 region (FR1f), with a new approach using a consensus primer against FR1 (FR1c), never previously described for diagnostic purposes, on DNA from 89 monoclonal B-cell proliferations (16 ALL, 28 CLL/PLL, 15 myelomas, 30 NHL). We obtained a detection rate of 70% for FR3, 64% for FR1f and 77% and 78% for FR256 and FR1c, respectively. Polyclonal lymphocytes and mature T cell malignancies tested negative for all systems. Differences in the detection rate were related not only to the choice of VH primer but also the JH primer(s) used and the pathological subtype. All strategies led to adequate detection of leukaemic DNA, whereas the detection rate in myeloma varied between strategies from 47 to 80% and that of follicular lymphoma from 13 to 63%. The lowest detection rates were observed in follicular lymphoma and in mature CD5 negative proliferations, reflecting the probable correlation between somatic mutation and PCR false-negativity. The combined use of FR1c and FR256 allowed detection in at least one system of 92% of cases overall and at least 75% in all pathological subtypes, thus providing a simple, reliable and rapid non-radioactive system for the detection of B cell clonality.
Leukemia 1995 Mar
PMID:Description of a novel FR1 IgH PCR strategy and its comparison with three other strategies for the detection of clonality in B cell malignancies. 753 68

The oncoprotein bcl-2 can be expressed in malignant plasma cells and might play a role in the prevention of corticosteroid-mediated apoptosis, thereby prolonging survival of the myeloma cells. We retrospectively investigated whether bcl-2 expression in bone marrow plasma cells measured by two-color fluorescence for immunoglobulin light chains would be related to survival duration in patients suffering from multiple myeloma. In all patients the large majority of plasma cells expressed bcl-2 (median 91%, range 74-100%). Contrary to our expectations, a tendency was observed toward higher percentages bcl-2+ plasma cells in patients with a long survival (more than 5 years, n = 9) vs patients who died from refractory myeloma within a year of diagnosis (n = 7). This tendency was found even when analysis was extended to include four patients in the short diagnosis group (n = 11) who had received chemotherapy prior to bone marrow examination.
Leukemia 1995 Jul
PMID:Bcl-2 protein expression is not related to short survival in multiple myeloma. 763 Feb 4

Osteolysis resulting in extensive bone damage is a major clinical manifestation of patients with multiple myeloma (MM). The mechanisms of bone resorption in MM are incompletely understood. The final pathway is the generation of activated osteoclasts within bone marrow (BM) microenvironment. To investigate the mechanisms of bone resorption in MM we established an experimental system that, including bone marrow (BM) stromal cells and bone slices, closely mimicks in vitro the in vivo BM microenvironment. Peripheral blood mononuclear cells (PBMC) from nine patients with MM, three monoclonal gammopathy of undetermined significance (MGUS), and nine normal controls were cultured in this system. PBMC from patients with aggressive and bone devastating MM gave rise to multi-nucleated cells with the morphology and phenotype of osteoclasts. These cells induced bone resorption in vitro which was inhibited by the addition of calcitonin. No bone resorption was observed in cultures of PBMC from patients with MM and limited bone damage, with MGUS and from normal subjects. These findings indicate that patients with aggressive MM have a population of circulating precursors that develop into functionally active osteoclast-like cells once they come in contact with the BM microenvironment. These cells may contribute to the wide-spread and generalized bone erosion observed in the patients.
Leukemia 1995 Aug
PMID:Osteoclast precursors circulate in the peripheral blood of patients with aggressive multiple myeloma. 764 30

Multiple myeloma (MM) is defined as a tumoral expansion of plasma cells occurring in the bone marrow and sometimes in the peripheral blood (plasma-cell leukemia, PCL). Many reports have demonstrated a clonal expansion of B cells bearing the same idiotypic determinants as the myeloma protein (idiotypic B cells) in MM, suggesting that they could belong to the malignant clone. In order to investigate whether the B-cell population is a malignant component or not, either in the peripheral blood of patients with PCL or in the bone marrow of patients with MM, we derived B-cell lines by infecting, with the Epstein-Barr virus (EBV), cultures in limiting dilution of mononuclear cells from six patients. A limiting dilution culture was used to prevent the elimination of slowly proliferating clones by the more rapidly dividing ones, and thus to get the most exact representation of the B-cell repertoire of these patients. The cloning efficiency of the EBV-infected cells was similar in patients and healthy individuals (range: 1 in 100 to 1 in 1650 B cells). All of the clones obtained from a single patient exhibited different clonal immunoglobulin gene rearrangements (IGR), proving the validity of our cloning technique. No tumoral clones (61 clones analysed) showed the IGR pattern specific of autologous myeloma cells. These results indicate that malignant plasma cells cannot be immortalized with EBV. These results show that, if malignant B cells (pre-switch or post-switch) exist, they could be present only in a minor population, and the corollary of this is that there is a major population of non-malignant B cells in the sites of tumoral proliferation of patients with MM. This is remarkable in view of numerous reports showing a profound defect of the polyclonal B lymphopoiesis in these patients, and even an absence of B lymphocytes. Thus, these results challenge the existence of a major compartment of malignant idiotypic B cells and favor the hypothesis of non-malignant B cells sharing cross-reactive idiotypes with the autologous myeloma protein.
Leukemia 1993 Apr
PMID:Analysis of the B-cell compartment in plasma cell leukemia and multiple myeloma: immunoglobulin gene rearrangement of EBV-infected B-cell lines. 768 18

Positive selection of CD34+ cells has applications in diagnostic pathology, in peripheral blood and bone marrow transplantation, and in studies on the function and regulation of primitive haemopoietic stem cells. Antibody-coated magnetic microspheres (dynabeads) can be used to isolate these cells by positive selection procedures. However, the advantages of using dynabeads in some positive selection protocols are compromised by the retention of the beads on the cells. We present a protocol which allows the rapid chemical release of the beads from positively sorted cells. The murine immunoglobulin (Ig) G1 CD34 antibody, QBEND/10, was immobilised onto dynabeads as part of a three-layered immune complex: QBEND/10 was attached to F(ab')2 anti-mouse immunoglobulin antibody fragments, which were immunologically bound to a mouse IgG1 myeloma protein. The myeloma protein covalently bonded the triplex to the beads. Thus, disulphide bonds in the hinge region of the F(ab')2 could be reduced with 10 microM dithiothreitol and CD34+ cells released within 20 min. Purified cells can be re-phenotyped by multiple markers and subsets identified. Purity of 97%, recovery of > 50%, and viability over 90% of the CD34+ cells was readily achieved. Furthermore, granulocyte-macrophage colony-forming cells were retained in the positive fraction. This methodology can be used to purify other cell types, including T and B lymphocytes.
Leukemia 1993 Jun
PMID:Rapid positive selection of CD34+ cells using magnetic microspheres coated with monoclonal antibody QBEND/10 linked via a cleavable disulphide bond. 768


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