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)

Interleukin-16 (IL-16) is a chemoattractant of CD4+ lymphocytes, and it has been implicated in the pathogenesis of various inflammatory diseases. There is evidence that it may have a role in multiple myeloma (MM). In the present study, we determined the serum level of IL-16 both before and after treatment of MM and related it to inflammatory markers and survival. Forty-eight newly diagnosed MM patients were included in the study. Disease stage was defined using the Durie-Salmon classification system (10 patients were in stage I, 19 in stage II, and 19 in stage III). After standard treatment, 22 patients reached the plateau phase and were re-evaluated. The following serum parameters were measured: IL-16, IL-6, alpha-1 antitrypsin (alpha1AT), and C-reactive protein (CRP). Survival was determined as the number of months elapsed since original diagnosis. The mean +/- SD of serum IL-16 was 343 +/- 195 pg/ml in the pre-treatment MM group and 101 +/- 30 pg/ml in the control group. All measured parameters were higher in the patient group compared to healthy controls. Furthermore, IL-16, IL-6, alpha1AT, and CRP were significantly increased with increasing stage of disease, from stage I to stage III (P<0.01). All parameters decreased significantly following effective chemotherapy (P<0.002). Patients with a high level of IL-16 (>430 pg/ml) displayed an inferior survival time in comparison to those with lower levels of IL-16. In the pre-treatment group, IL-16 correlated with alpha1AT and IL-6 (r=0.374, P<0.01 and r=0.454, P<0.002, respectively). IL-16 may play a role in multiple myeloma; however, further functional studies are required.
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PMID:Serum level of interleukin-16 in multiple myeloma patients and its relationship to disease activity. 1475 77

The frequency and prognostic relevance of translocations t(11;14) and t(4;14), the most common translocations involving the immunoglobulin heavy chain (IgH) gene in multiple myeloma (MM), were investigated in 128 patients treated with intensive chemotherapy and autologous stem cell transplant. Myeloma cells were identified by cytoplasmic light chain immunofluorescence combined with fluorescence in situ hybridization (cIg-FISH) for detection of translocations t(11;14) and t(4;14). Overall, t(11;14) was detected in 16 of 125 (12.8%) and t(4;14) in 15 of 120 (12.5%) patients. Progression-free and overall survivals were similar for patients with or without t(11;14). However, patients with t(4;14) had significantly shorter progression-free (median 9.9 months vs. 25.8 months; P = 0.0003) and overall survivals (median 18.3 months vs. 48.1 months; P < 0.0001) than patients without t(4;14). The t(4;14) was associated with IgA and t(11;14) with light chain MM. There was no association between the t(11;14) or t(4;14) and other biological parameters including age, gender, haemoglobin, beta-2 microglobulin, C-reactive protein, calcium, creatinine, albumin, or the percentage of bone marrow plasma cells. Multivariate analysis identified t(4;14) as the only adverse prognostic factor for both progression-free survival and overall survival. Our results indicate that the t(4;14) detected by cIg-FISH is associated with a poor prognosis in MM patients receiving intensive chemotherapy and autotransplant.
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PMID:The t(4;14) is associated with poor prognosis in myeloma patients undergoing autologous stem cell transplant. 1501 70

Conflicting data are reported on the clinical significance of cyclin D1 deregulation in multiple myeloma. The aim of this study was to evaluate the incidence and prognostic significance of cyclin D1 expression and p53 mutations in multiple myeloma, as well as the relationship of their expression with selected clinical data, histological features, and proliferative activity of myeloma cells. We analyzed bone marrow biopsy specimens obtained from 59 patients with newly diagnosed multiple myeloma. Expression of cyclin D1 and p53 was analyzed using standard immunohistochemical method of B5-fixed and routinely processed paraffin-embedded bone marrow specimens. Cyclin D1 was overexpressed in 14/59 (27%) and p53 in 5/59 (8.5%) specimens. There was no significant correlation between cyclin D1 overexpression and age, gender, clinical stage (Durie-Salmon classification), extent of osteolytic lesions, type of monoclonal protein, hemoglobin concentration, platelet count, serum concentration of creatinine, calcium, C-reactive protein, and beta2-microglobulin. No association was observed between the expression of cyclin D1 and the extent of bone marrow infiltration, histological grade, proliferative activity index (measured with Ki-67 immunoreactivity) and response to therapy. No significant difference was observed regarding overall survival between cyclin D1 positive and cyclin D1 negative patients (29 vs 36 mo, p = 0.76). Results of this study did not revealed prognostic significance of cyclin D1 overexpression in multiple myeloma. Mutations of p53 gene are rare events in myeloma, suggesting their limited role in the pathogenesis of the disease.
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PMID:Immunohistochemical analysis of cyclin D1 and p53 in multiple myeloma: relationship to proliferative activity and prognostic significance. 1503 17

Interleukin-6 (IL-6) and C-reactive protein (CRP, a surrogate marker for IL-6) are important in monoclonal gammopathy of undetermined significance (MGUS) and myeloma. Smoking and obesity may elevate CRP levels, while statins decrease CRP levels. A case-control study in 200 MGUS patients found that statin use, smoking history and obesity do not affect MGUS progression.
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PMID:Effect of statins, smoking and obesity on progression of monoclonal gammopathy of undetermined significance: a case-control study. 1513 36

Bone disease is a common feature of multiple myeloma (MM). The goal of this study was to assess the prognostic significance of urinary markers of bone metabolism in MM. Urinary levels of total pyridinoline (T-Pyd), deoxypyridinoline (T-Dpd), crosslinked N-telopeptide (Ntx), C-telopeptide (Ctx) of type I collagen and immunologic free deoxypyridinoline (f-Dpd) were assessed in 82 consecutive, previously untreated MM patients (aged 65-75 years) diagnosed between June 1995 and December 1998. A correlation between disease stage according to the Durie-Salmon classification and T-Pyd (p=0.034) and T-Dpd (p=0.007) was observed, while T-Pyd (p=0.015) and to a lesser extent f-Dpd (p=0.081) were correlated to bone involvement measured by plain X-ray. None were correlated to M-component or magnetic resonance imaging (MRI). In univariate analysis high T-Pyd (p=0.007), T-Dpd (p=0.027), f-Dpd (p<0.001), and Ctx (p=0.011) were associated with shorter overall survival, whereas only f-Dpd (p=0.0025) was associated with a shorter disease-free survival. In multivariate analysis, C-reactive protein and f-Dpd were independent prognostic factors for overall survival. This retrospective analysis defined new independent prognostic indicators of survival in patients with newly diagnosed myeloma. Indeed, urinary markers of bone resorption can easily be measured at diagnosis and have independent prognostic significance to refine the prognosis of MM patients.
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PMID:Prognostic value of urinary pyridinium crosslinks and their derivatives in multiple myeloma. 1533 98

We investigated the relevance of p53 deletions to the clinical outcome of patients with multiple myeloma (MM) treated with high-dose chemotherapy and autologous stem cell transplantation. Hemizygous p53 gene deletions were detected by fluorescence in situ hybridization in 10 of 105 (9.5%) patients studied. p53 deletions were associated with higher serum calcium (P = .0062) and creatinine (P = .013) levels, but there were no association with patient age, gender, beta2-microglobulin, C-reactive protein, hemoglobin, albumin or bone lytic lesions, or immunoglobulin isotype. There were no associations of p53 deletions with 13q deletions or translocations t(11;14) or t(4;14). Patients with p53 deletions had significantly shorter progression-free (median, 7.9 versus 25.7 months, P = .0324) and overall survival (median, 14.7 versus 48.1 months, P = .0008) than patients without a p53 deletion. A multivariate analysis confirmed p53 deletion was an independent prognostic factor predicting shortened progression-free (P = .0009) or overall survival (P = .0002) in patients with MM after high-dose chemotherapy and autologous stem cell transplantation.
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PMID:p53 gene deletion detected by fluorescence in situ hybridization is an adverse prognostic factor for patients with multiple myeloma following autologous stem cell transplantation. 1533 49

The application of high-dose treatment with autologous stem cell transplant(s) has improved survival, when compared to standard treatment, in patients with multiple myeloma. However, this benefit is mostly enjoyed by specific patient subgroups characterized by the absence of high-risk disease features. High-risk features are, first and foremost, the detection of unfavorable cytogenetic abnormalities (chromosome 13 deletion, hypodiploidy and myelodysplastic-type abnormalities in an otherwise typical myeloma karyotype) prior to treatment; elevated serum lactate dehydrogenase and C-reactive protein levels at diagnosis and high beta-2 microglobulin levels prior to transplant also convey poor prognosis, although they account for less variability of the observed outcome than the cytogenetic abnormalities. While high-dose treatment with autologous stem cell transplant(s) can cure a sizable minority of patients with low-risk disease features and significantly prolongs survival in others with similar characteristics, patients with high-risk features are virtually incurable and their survival benefit is much less pronounced. As the tremendous clinical variability of myeloma can now be traced to its underlying genetic abnormalities, routine cytogenetic analysis at diagnosis and relapse are absolutely indicated. Based on this stratification, high-risk patients are excellent candidates for novel therapeutic approaches, such as planned non-myeloablative allogeneic transplants following an autologous transplant.
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PMID:Chromosome 13 deletion/hypodiploidy and prognosis in multiple myeloma patients. 1535 86

We have analysed a series of 96 patients with multiple myeloma (MM) to the purpose to verify the prognostic meaning of the beta2-microglobulin (B2M) and the validity of the staging systems proposed by Bataille and Jacobson who use the B2M respectively associated to the serum C-reactive protein (CRP) and to the serum albumin. In our series of patients the serum level of B2M at the diagnosis was directly correlated with the myelomatous cellular mass. We have found besides an inverse correlation between B2M and survival. Also the serum level of CRP was inversely correlated with the survival, while a direct correlation was found between the serum albumin and the survival: ipoalbuminemia was confirmed as a predictive index of short survival. Staging our patients with MM according to the proposal of Bataille, we identified also in our series three prognostic groups with different median survival: respectively 72, 40 and 18 months. Applying finally the staging proposal of Jacobson to our series, four stages were individualized, with median survival respectively of 70, 52, 26 and 10 months. We confirm the prognostic value of the B2M in MM.
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PMID:[Prognostic value of serum beta2-microglobulin in multiple myeloma]. 1584 67

We detected circulating plasma cells (PCs) by flow cytometry in 302 patients with newly diagnosed multiple myeloma (MM) by gating on CD38+CD45- cells. The number of circulating PCs per 50 000 mononuclear cells was reported. In 80 (27%) patients, no circulating PC were seen; 106 (35%) patients had 1 to 10 and 115 (38%) patients had more than 10 circulating PCs. Median overall survival for the 302 patients was 47 months. Patients with 10 or fewer circulating PCs had a median survival of 58.7 months, whereas patients with more than 10 circulating PCs had a median survival of 37.3 months (P = .001). On multivariate analysis, the prognostic value of circulating PCs was independent of beta2-microglobulin, albumin, and C-reactive protein. There was only a weak correlation between tumor mass and circulating PCs, suggesting that the appearance of circulating PCs may be a reflection of tumor biology. We conclude that the number of circulating PCs measured by flow cytometry in patients with newly diagnosed MM is an independent predictor of survival.
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PMID:Circulating plasma cells detected by flow cytometry as a predictor of survival in 302 patients with newly diagnosed multiple myeloma. 1596 15

In the present study the immunohistochemical expression of Bcl-xl, a downstream target of the IL-6-controlled signal transducer and activator of transcription-3 (Stat3) was studied in 40 multiple myeloma (MM) cases before treatment and 11 MM patients at relapse. Correlation analysis was performed between Bcl-xl expression, C-reactive protein (CRP) level, beta-2-microglobulin (beta2m), microvessel density (MVD), and clinical outcome. Before treatment 28 (70%) patients demonstrated a Bcl-xl expression similar to normal plasma cells ("normal pattern"), while 12 (30%) patients demonstrated an elevated expression in a subgroup of the malignant plasma cells. At relapse, no change in Bcl-xl expression was observed as compared to pretreatment sample. No correlation was observed between the Bcl-xl expression and the level of CRP and b2m. In addition, no significant correlation was observed between the Bcl-xl expression and the MVD, but MVD was significantly increased as compared to normal bone marrow biopsy specimens (p=0.02). Patients with an elevated or normal Bcl-xl expression showed no statistically significant difference in overall and event-free survival. In summary, these data indicate that Bcl-xl is elevated in a subgroup of MM patients that so far did not correlate with CRP, b2m, MVD, and clinical outcome.
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PMID:Bcl-xl expression in multiple myeloma. 1596 82


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