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)

The isoelectric point (pI) of the major form of Bence-Jones protein excreted by 62 patients with myeloma and six with macroglobulinaemia was measured by combining isoelectric focusing with immunoblotting techniques. The distribution of the pI values for both kappa and lambda type proteins was bimodal, most falling in the ranges 5.0-6.0 and 7.0-7.5. Plasma creatinine and creatinine clearance and the urine excretion of alpha-1-microglobulin and beta-2-microglobulin were measured in 24 of the patients. These patients, who were free of additional factors known to have an association with the development of renal impairment, were followed up for a mean period of 16 months (range three to 28 months). It was found that renal impairment was not related to the pI of the Bence-Jones protein excreted.
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PMID:Renal impairment in myeloma: negative association with isoelectric point of excreted Bence-Jones protein. 246 54

The peripheral blood and bone marrow mononuclear cell immunophenotype was investigated in series of 41 patients with plasma cell dyscrasias (29 with multiple myeloma and 12 with monoclonal gammopathy of undetermined significance (MGUS) or solitary plasmacytoma). A statistically significant relationship between the presence of monotypic B-cells (MBC) in the peripheral blood and the paraprotein light chain isotype was found in the myeloma patients (P = 0.0025). MBCs were documented in 71% of patients with lambda paraproteins, compared with only 13% of patients with kappa paraproteins. The difference in MBC was independent of disease stage as well as of individual prognosticators such as haemoglobin, renal function, paraprotein size and beta-2-microglobulin, although lambda producers had significantly higher calcium levels than patients with kappa paraproteins (P = 0.03). A similar trend was also noted for MBC to be found more commonly in patients with lambda producing MGUS and solitary plasmacytoma. This phenomenon may account for the worse prognosis in patients with lambda paraproteins. In our hands, immunophenotypic detection of peripheral blood involvement in plasma cell dyscrasias is more sensitive than investigation of karyotype or immunoglobulin gene rearrangements.
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PMID:Circulating monotypic B-cells in multiple myeloma: association with lambda paraproteins. 250 24

Serum beta-2-microglobulin (beta 2M) has been suggested as the most powerful prognostic factor in multiple myeloma (MM). This paper investigates its ability to detect remission and relapse in individual patients. A correlation analysis was carried out between beta 2M and M component determinations, at diagnosis and monthly during follow-up in 21 consecutive MM patients with normal renal function. A statistically significant correlation was observed in 52.4% only. The lack of correlation in the remaining cases was due to low beta 2M production at diagnosis, or independent fluctuation of these 2 parameters. Serum beta 2M proved a much less reliable parameter for the detection of tumour variations than simpler M-component determination.
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PMID:Multiple myeloma: beta-2-microglobulin is not a useful follow-up parameter. 251 Apr 33

Interleukin-1 (IL-1), Interleukin-2 (IL-2) and soluble receptors for IL-2 (sIL-2R) play a crucial role in the immune response. IL-2 in particular is implicated not only in T-cell proliferation but also in normal B-cell proliferation and differentiation and in the development of B and T cell malignancies. We have assayed the serum levels of IL-1, IL-2 and sIL-2R in 12 patients with monoclonal gammopathy of undetermined significance (MGUS) and 44 patients with multiple myeloma (MM). Sera collected from 40 healthy blood donors were used for normal values, and sera from 33 medical volunteers over 48 years of age (median age 52 years) for normal IL-2 values in the elderly. Mean IL-2 serum values were 6.50 U/ml in MGUS and 4.97 U/ml in MM patients. There was a statistical significant elevation of IL-2 levels is both MM and MGUS patients when compared to both normal controls (p less than 0.001, Wilcoxon two tailed test). A significant difference in IL-2 levels (p less than 0.025) was also observed between MGUS and MM patients. The levels of serum IL-1 and sIL-2R were normal both in MGUS and MM patients. In 24 MM patients where the dosage of serum beta-2-microglobulin was available, a significant difference (p less than 0.01) in serum IL-2 levels was found between patients with beta-2-microglobulin greater than 6 micrograms/ml and less than 6 micrograms/ml. Pathogenic mechanisms as well as their possible clinical significance are discussed.
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PMID:High serum interleukin-2 levels in patients with monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma. 258 1

Although conferring a grave prognosis in patients with malignant lymphoma, high levels of serum lactic dehydrogenase (LDH) are usually not seen in patients with multiple myeloma, a more indolent tumor composed mainly of B cells in their terminal stage of differentiation. Thus, only 2 of 118 patients in earlier phases of myeloma showed marked LDH elevations to more than 500 U/L, whereas such abnormalities were present in 12 of 64 patients with advanced disease progressing despite treatment with vincristine, doxorubicin (Adriamycin), dexamethasone (VAD) (median LDH level, 700 U/L). High LDH levels were associated with high serum levels of beta-2-microglobulin, hypercalcemia, extraosseous disease features, a short preceding clinical course as well as a short subsequent survival time. A poor prognosis was also noted in patients with lower LDH in whom marked increments were induced by high-dose chemotherapy; thus, LDH elevations to greater than 300 U/L present before or found after high-dose cytotoxic therapy were observed in about 50% of patients with VAD-resistant myeloma and define a new clinical entity with features of extraosseous disease and an unusually aggressive course ("high-grade myeloma"). The shorter survival of newly diagnosed patients with high-normal compared with those with low-normal LDH levels (less than 200 U/L), regardless of tumor mass, suggests the presence in some patients of a tumor subpopulation with high LDH production that escapes growth control with standard treatment. Staging of multiple myeloma should therefore include measurements of serum LDH levels in addition to beta-2-microglobulin analysis and tumor mass estimation.
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PMID:High serum levels of lactic dehydrogenase identify a high-grade lymphoma-like myeloma. 264 15

This study describes the presence of small numbers of common acute lymphocytic leukaemia antigen (CALLA, CD10)-positive lymphocytes in the peripheral blood of patients with multiple myeloma. A significant correlation (0.001 less than P less than 0.01) was found between the lack of light chain isotype suppression (LCIS), which is characteristic of progressive myeloma, and the presence of CALLA-positive lymphocytes. Sixty patients with multiple myeloma, four with benign monoclonal gammopathy (BMG) and seven with solitary plasmacytoma (SP) were monitored in this study. Nineteen of the patients with multiple myeloma demonstrated LCIS, of which only three were found to have CALLA-positive lymphocytes. Of the 41 patients with multiple myeloma who did not have LCIS, 20 (49%) had CALLA-bearing lymphocytes. None of the patients with BMG or SP demonstrated LCIS or were found to have CALLA-bearing lymphocytes in their blood. Forty-four of the patients with multiple myeloma were also monitored for serum beta-2-microglobulin (SB2M levels. There was no correlation between the SB2M and either LCIS or CALLA-positivity. Detection of CALLA-positive lymphocytes in the blood of patients with multiple myeloma may be an early marker of the onset of progressive disease. The correlation of CALLA expression on lymphocytes with lack of LCIS provides further evidence for the operation of immunoregulatory systems in these patients.
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PMID:Multiple myeloma: the relationship between CALLA (CD10) positive lymphocytes in the peripheral blood and light chain isotype suppression. 295 9

In this study we have investigated the relationship between the labelling index of plasma cells, the expression of CD38 positive lymphocytes in the peripheral blood, and light chain isotype suppression. This study confirms the relationship between plateau-phase disease and light chain isotype suppression (LCIS) and documents an inverse relationship between LCIS and CD38 positive lymphocytes (.001 less than P less than .01), which is similar to the relationship we have described with the expression of CD10 positive lymphocytes. PCA-1 is rarely expressed in the peripheral blood of patients with myeloma and does not fulfill a role as a marker of active vs. stable disease. There is no relationship between the labelling index of plasma cells and LCIS, because many patients can enter a stage of progressive disease and yet have a labelling index of less than 1% at that time, although a labelling index less than 1% is present in the majority of patients with LCIS. beta-2-microglobulin (beta 2M) also fails to differentiate these two phases of disease in myeloma and does not have a relationship with LCIS, CD38 expression, or CD10 expression. These data suggest that myeloma, like chronic granulocytic leukemia (CGL), can be considered as having two phases of disease: a stable or chronic phase disease, as identified by the presence of LCIS, the absence of CD10 and CD38 positive lymphocytes in the peripheral blood, and a low labelling index, and progressive disease, which is associated with the loss of LCIS and of, CD10 and CD38 positive lymphocytes in the peripheral blood and a high labelling index, although in many cases of progressive disease, the labelling index may also be low. beta 2M does not differentiate between these states.
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PMID:Multiple myeloma: relationship between light chain isotype suppression, labelling index of plasma cells, and CD38 expression on peripheral blood lymphocytes. 305 44

Monoclonal antibodies (MoAbs) reacting with bovine leukocyte membrane antigens have been prepared by fusion of mouse myeloma cells (SP2/0.Ag.14) and spleen cells of mice immunized with various cell types. Three of these MoAbs detected membrane components showing the typical structure of class I MHC molecules; indeed, immunoprecipitation studies revealed that these components were proteins composed of two subunits of 44,000 and 12,000 daltons apparent molecular weight. The density of these antigens in the cells of various leukocyte lineages was determined by solid phase radioimmunoassay, immunogold staining and cytofluorometry. Their expression seemed similar to that of class I molecules in other species, namely heavy on the mononuclear blood cells and weaker on the neutrophils and platelets. The eosinophils appeared more positive than the neutrophils, while the erythrocytes were negative. Cross-inhibition and sequential immunoprecipitation experiments demonstrated that these MoAbs recognised different epitopes either on a single molecule or on cross-reacting molecules. One antibody appeared to be raised against the monomorphic bovine beta-2-microglobulin, while the two other antibodies detected the heavy chain of polymorphic class I-like products. The authors propose that the BoLA class I polymorphism should be studied by determination of the fixation ratio of the monomorphic anti-beta 2M versus the polymorphic anticlass I antibodies amongst the animals.
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PMID:Production and characterization of monoclonal antibodies raised against BoLA class I antigens. 309 53

Simultaneous evaluation of bone marrow plasma cell thymidine labelling index (LI) and serum beta-2-microglobulin (SB2M) was performed in 146 patients with multiple myeloma (MM) or monoclonal gammopathy of undetermined significance (MGUS). Eighty patients had MM on diagnosis, 11 were in relapse and 12 were in remission phase; 43 patients had MGUS. All the evaluated patients had normal renal function with a creatinine level less than 1.4 mg%. Overall there was no direct correlation between LI% and SB2M. LI% best reflected the proliferative capacity of the tumor clone itself being less than or equal to 1% in MGUS and MM in remission, but greater than 2% at relapse of MM. SB2M correlated best with the stage of disease and tumor burden. These two factors therefore have different clinical utility: LI is a useful parameter to detect disease stability (e.g., MGUS) or highly proliferative disease (aggressive MM at diagnosis or early relapse). SB2M remains the best single predictor of patient tumor burden and associated survival duration.
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PMID:Lack of correlation between plasma cell thymidine labelling index and serum beta-2-microglobulin in monoclonal gammopathies. 312 89

Measuring serum beta-2-microglobulin (B2M) in 90 patients with multiple myeloma (MM) from diagnosis to death (83 cases), or to the terminal phase of their disease (7 cases), we have obtained evidence that 9% of them retained normal serum B2M levels during the whole of their follow-up. This was observed in 6 IgA MM, in one light chain MM only and in one non-secretory MM. These data suggest a lack of B2M production and/or secretion by some myeloma tumors. This could limit the use of B2M as clinical marker in MM.
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PMID:Unexpected normal serum beta-microglobulin (B2M) levels in multiple myeloma. 330 2


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