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)

To evaluate the possibility that genetic factors contribute to the excess rates of multiple myeloma among blacks, serological typing of human leukocyte antigens (HLA) was conducted for black and white male patients and controls who participated in a large population-based case-control interview study. Forty-six black cases, 88 black controls, 85 white cases, and 122 white controls were typed for the Class I antigens (HLA-A, -B, -C) and for the Class II antigens (HLA-DR, HLA-DQ). Black cases had significantly higher gene frequencies than black controls for Bw65, Cw2, and DRw14, while white cases had higher gene frequencies than white controls for A3 and Cw2 and blanks at the DR and DQ loci. Further analysis of the association between Cw2 and multiple myeloma revealed relative risks of 5.7 (95% confidence interval = 1.5-26.6) and 2.6 (95% confidence interval = 1.0-7.2) for blacks and whites, respectively. The frequency of Cw2 in black and white controls was similar. These findings suggest that the Cw2 allele enhances the risk of myeloma in blacks and whites but do not explain the higher incidence of this cancer among blacks. The study also suggests that undefined DQ antigens may play an etiological role, supporting the need for further research into the immunogenetic determinants of myeloma.
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PMID:HLA and multiple myeloma among black and white men: evidence of a genetic association. 130 2

A 72-year-old man presented with a left testicular tumor and underwent orchiectomy. The tumor was massively infiltrated with myeloma cells bearing monoclonal cytoplasmic IgD lambda. Three months after orchiectomy, he developed huge abdominal masses and subsequently ascites containing numerous myeloma cells. An IgD-secreting myeloma cell line, designated delta-47, was established from the ascites. This cell line expressed CD4 and CD38, but lacked Fc and complement receptors, surface immunoglobulin, CD19, HLA-DR, and PCA-1. CD30 was detected on the cultured cells but not on the ascites tumor cells. Delta-47 cells secreted the same immunoglobulin (IgD lambda) as was found in the patient's serum. The light chain had a molecular weight of 35 kD which was larger than that of the normal light chain. Chromosome analysis of delta-47 revealed an aneuploid karyotype with complex abnormalities including 1q+, 2p+, and 14q+. To our knowledge, this is the only IgD-secreting myeloma cell line and would provide a useful tool for the study of IgD production and IgD myeloma.
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PMID:IgD myeloma presenting as a testicular tumor: establishment and characterization of an IgD-secreting myeloma cell line. 132 2

We show that a highly aggressive subclone of murine BCL-1 B-lineage leukemia expresses a single 2.4-kb transcript hybridizing to the human CD19 cDNA probe and reacts strongly with the anti-human CD19 monoclonal antibodies (MoAb) B43, B4, Leu-12, and J3-119. In contrast to their strong reactivity with anti-human CD19 MoAb, BCL-1 cells show no reactivity with MoAb directed against human CD22, CD72, HLA-DR, IgD, or IgM. Western blot analysis of BCL-1 whole cell lysates with the anti-human CD19 MoAb J3-119 showed a single 69-Kd protein band, which was not detected by the negative control MoAb G19.4 (anti-CD3). In contrast to BCL-1 cells, normal BALB/c splenocytes or mouse splenocyte/myeloma hybridoma cell lines did not (1) express any transcripts that hybridized to the human CD19 cDNA probe, (2) react with B43/anti-CD19 MoAb, or (3) express the 69-Kd protein that reacts with the anti-human CD19 MoAb J3-119. Murine BCL-1 B-cell leukemia thus provides a unique model of disseminated B-lineage leukemia to evaluate the antileukemic efficacy of anti-CD19 immunotoxins. This model was subsequently used to evaluate the in vivo homing ability, pharmacokinetics, and antileukemic efficacy of B43 MoAb conjugated to the plant hemitoxin pokeweed antiviral protein (PAP). B43-PAP immunotoxin (1) showed strong and antigen-specific reactivity with BCL-1 cells, (2) promptly penetrated the spleens of leukemic mice, (3) rapidly reduced the BCL-1 leukemia burden of leukemic mice and, most importantly, (4) improved survival. Finally, B43-PAP immunotoxin was more effective against BCL-1 leukemia than 700 cGy (LD100/30) total body irradiation (TBI) followed by syngeneic bone marrow transplantation (BMT).
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PMID:In vivo efficacy of B43 (anti-CD19)-pokeweed antiviral protein immunotoxin against BCL-1 murine B-cell leukemia. 137 9

A 78-year-old woman complaining of a neck mass underwent right hemithyroidectomy. The 7 x 6 cm thyroid tumor consisted predominantly of mildly atypical, epithelial membrane antigen-positive plasma cells and scattered lymphoid follicles. Features of follicular colonization (plasma cell infiltration into germinal centers) were noted. Numerous CD45RO-positive reactive T cells and a smaller number of CD20-positive blast-like B cells were also distributed among the plasma cell infiltrate. IgG, kappa-type monoclonality with J-chain reactivity was identified in the plasma cells, including those in the lymphoid follicles. The association of pre-existing lymphocytic thyroiditis was confirmed histologically in the non-tumorous thyroid tissue. The tumor exhibited deposition of reticulin fiber-rich, amorphous eosinophilic substances, provoking pronounced foreign body reactions. The deposit, polytypically immunoreactive for immunoglobulin gamma-, mu-, kappa- and lambda-chains, beta 2-microglobulin and HLA-DR, was scarcely reactive upon amyloid staining, and consisted ultrastructurally of electron-dense, non-fibrillar material and entrapped collagen fibers. Multiple myeloma was ruled out by laboratory, histologic and clinical examinations. The possible categorization of this extramedullary plasmacytoma of the thyroid within low-grade B cell lymphoma of the mucosa-associated lymphoid tissue (MALT) is discussed.
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PMID:Extramedullary plasmacytoma of the thyroid, associated with follicular colonization and stromal deposition of polytypic immunoglobulins and major histocompatibility antigens. Possible categorization in MALT lymphoma. 147 63

A cell line of plasma cells with high ammonia (NH3) production (KHM-4) was established from a patient with multiple myeloma complicated by hyperammonemia and abnormal serum concentrations of amino acids. Surface marker studies of KHM-4 cells showed that the cells were positive for cytoplasmic immunoglobulins (IgA kappa), HLA-DR, and T 10. Secretion of ammonia by the KHM-4 cells was detected by the addition of L-glutamine and L-arginine into the culture medium of amino acid-free RPMI 1640. In the presence of L-glutamine, KHM-4 cells secreted a greater amount of ammonia than the T cell line, CEM. However, production of ammonia by L-arginine was not observed in other cell lines. These observations provide evidence for the existence of a peculiar amino acid metabolism in the myeloma cells causing hyperammonemia and serum amino acid disturbance.
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PMID:Human myeloma cell line (KHM-4) established from a patient with multiple myeloma associated with hyperammonemia. 161 Nov 84

A new human plasma cell line, UMJF-2, has been derived from the bone marrow of a patient with multiple myeloma. Morphological studies disclosed large nucleoli, moderate numbers of mitochondria, and scant endoplasmic reticulum consistent with a plasmablastic morphology. The cells have immunologic characteristics of early plasma cells, including intense expression of cytoplasmic IgG-lambda and weaker, but discernible, expression of surface IgG-lambda. Cell surface antigens defined by the monoclonal antibodies OKT10 (CD38) and PCA-1, characteristic of mature plasma cells, and B1 (CD20), B4 (CD19), and I-2 (HLA-DR), characteristic of earlier stages of B-lymphocyte differentiation, are present on UMJF-2 cells. Cytogenetic studies reveal the presence of trisomy 12. UMJF-2 does not contain the Epstein-Barr virus by Southern blot analysis. Tissue culture media conditioned by these cells contains a soluble immunosuppressive factor, capable of inhibiting pokeweed mitogen induced IgM secretion by normal human B-lymphocytes. UMJF-2 provides a model for the study of the pathogenesis of polyclonal hypogammaglobulinemia in human multiple myeloma.
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PMID:Characterization of a new human multiple myeloma cell line, UMJF-2, which suppresses antibody production by B-lymphocytes in vitro. 164 57

In 112 untreated myeloma patients we have analysed the immunophenotype of plasma cells both by immunofluorescence (IF) and immunocytochemistry (APAAP). Both techniques yielded similar results pointing to an important degree of heterogeneity in antigenic expression not only between different patients but also within the same patient. The expression of CD38 and Han-PC1 antigens (Ags) was almost constant (greater than 90% positive cases), while CD9 was detected in 66% of the cases. On the other hand, less than one third of patients were positive for CD10, CD20 and HLA-DR and generally with a weak expression (less than 30% positive plasma cells). In occasional cases plasma cells were weakly positive for the myelomonocytic markers CD13 (9%), CD15 (25%) and CD14 (6%). The possibility that this heterogeneity might be the result of different stages of differentiation of the neoplastic clone is suggested both by the positive correlation in the expression of some of these antigens (CD10, CD9, CD20, HLA-DR) and by the relationship between CD10 and myeloid antigens with immature plasma cell morphology. Finally, the cALLA antigen does not seem to be of significant value in predicting survival. Moreover, none of the other markers explored showed a clear influence in the course of the disease, although the tendency towards a lower survival found for the CD20+ cases as well as the association of the expression of some antigens and advanced clinical stage, may warrant further studies in a larger series of patients.
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PMID:Immunophenotypic heterogeneity of multiple myeloma: influence on the biology and clinical course of the disease. Castellano-Leones (Spain) Cooperative Group for the Study of Monoclonal Gammopathies. 170 97

Recent studies in multiple myeloma indicate that molecules associated with different haematopoietic lineages may be expressed aberrantly by myeloma cells. In order to investigate this phenomenon further, we studied the immunophenotype of bone marrow cells from 21 patients with multiple myeloma using a panel of monoclonal antibodies against T,B, myelomonocytic, and natural killer (NK)-cell antigens. Leu-19/NKH1 (CD56), a molecule identical to N-CAM, which is normally expressed by neuroectodermal and NK cells, was found in 13 patients (62%). Dual-parameter flow cytometry was used to correlate N-CAM positivity with DNA aneuploidy or cytoplasmic immunoglobulin expression as markers of myeloma cells. When N-CAM was found positive, other haematopoietic antigens were expressed only in three out of 13 cases (23%). In contrast, myeloma cells not expressing N-CAM frequently exhibited pre-B cell markers, myeloid antigen, and HLA-DR, respectively (seven out of eight cases, 88%). Six out of eight N-CAM-negative myelomas were of the IgG lambda isotype, otherwise no clearcut association with basic clinical and laboratory parameters was noted. We conclude that N-CAM expression is a common finding in multiple myeloma. Whether its expression and the observed antigenic heterogeneity is just a manifestation of malignancy or N-CAM may play a role in the biology of multiple myeloma regarding tumour cell spread, remains to be explained.
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PMID:Expression of the neural cell adhesion molecule (CD56) by human myeloma cells. 170 37

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

Recombinant human granulocyte/macrophage colony-stimulating factor (rhGM-CSF) was administered to a patient with multiple myeloma (IgA, stage IIA) who had a chemotherapy-induced bone marrow aplasia with granulocytopenia complicated by severe pneumonia and septicemia. The rhGM-CSF was given as i.v. infusions, 300-400 micrograms daily, for three weeks. The patient responded both hematologically and clinically with improved granulocyte counts and clearance of massive pulmonary infiltrates. We also observed a partial remission of the myeloma with decreasing s-IgA levels and reduced plasma cell infiltration of the bone marrow during a period of up to four months after the rhGM-CSF treatment. Immunological studies performed during and after cytokine administration showed an increase in serum interleukin-2 (IL-2) levels and HLA-DR positive T-lymphocytes indicating an activation of the immune system. It is suggested that rhGM-CSF induced immunological changes which may have contributed to the partial regression of the myeloma.
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PMID:Increase of serum interleukin-2 and regression of myeloma after rhGM-CSF treatment of drug induced bone marrow aplasia. 193 5


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