Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:O76050 (neu)
 3,969 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The expression of 6 different oncoproteins and 2 tumour suppressor gene products in the plasma cells of 63 bone marrow samples was used to determine a profile of the oncogenic phenotype of patients with multiple myeloma. Dual label flow cytometry after periodatelysine paraformaldehyde fixation was used to detect cell surface phenotype and intracellular protein expression simultaneously. The normal range for both the incidence and intensity of expression was determined for each protein by analysing plasma cells (high CD38 intensity) in 22 normal bone marrow samples. The percentage of myeloma patients with a greater than normal incidence of plasma cells expressing these proteins was 53% for c-myc, 28% for Rb, 28% for bcl-2, 27% for c-fos, 24% for p53 wild, 22% for p53 mutant, 13% for c-neu and 13% for pan-ras. When a panel of 8 antibodies was used, 82% of the samples (n = 28) had an increased incidence of expression by at least one oncoprotein or tumour suppressor gene product. The 5 patients with a normal incidence of expression of all 8 proteins were in plateau stage and 4 had not received chemotherapy for more than 12 months. The number of patients with an increased incidence of expression by 2 or more oncoproteins was significantly greater (X2 = 9.0; p < 0.005) in progressive disease (55%) than in stable disease (14%) but there was no specific phenotype pattern associated with progressive disease. All 6 oncoproteins and both tumour suppressor gene products had a greater incidence and intensity of expression in progressive than in stable disease. The expression of c-myc oncoprotein correlated with c-myc mRNA expression in the same samples (n = 10) but c-myc did not correlate with either the plasma cell labelling index (r = -0.15) nor serum thymidine kinase (r = 0.10). Our results suggest that there is a heterogeneous, non-systematic but almost universal presence of activated oncogenes and tumour suppressor genes in the plasma cells of patients with multiple myeloma and that disease progression is associated with the accumulation of a variety of secondary genetic changes which confer increased malignant behaviour.
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PMID:The oncoprotein phenotype of plasma cells from patients with multiple myeloma. 769 21

An 83-year-old male was admitted with a right pleural effusion and generalized lymphadenopathy. Serum LDH level was elevated to 801 IU/L, and the pathological diagnosis from inguinal lymph node needle biopsy was malignant lymphoma (ML) of diffuse, large cell, non-cleaved type, according to the working formulation. The surface phenotypes of the malignant cells from the pleural effusion were analyzed by a fluorescent-activated cell sorter with a panel of monoclonal antibodies (MAbs). The ML cells coexpressed antigens detected by MAbs CD10 (CALLA), CD19, CD20, CD22, CD24, CD38, Ia, c-neu and surface immunoglobulin G kappa. A high expression of NRAS p21 was also detected by cytoplasmic immunofluorescence technique. The patient died 19 days later despite a combination of chemotherapy and intensive supportive therapy. From these findings it seems that c-neu may be a prognostic indicator not only for breast cancers but also for lymphoproliferative disorders. Further accumulation of such cases is needed.
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PMID:[Aggressive diffuse lymphoma with malignant pleural effusion expressing c-erbB-2 (neu) oncogene products]. 810 89

The dysregulation of specific oncogenes due to either mutation or activation has previously been reported in a small number of patients with myeloma but the extent of oncogene dysregulation during the course of the disease is not known. The oncoprotein phenotype of plasma cells in 146 bone marrow samples from 81 patients with multiple myeloma was determined by dual colour flow cytometry using a predetermined panel of 8 monoclonal antibodies. High intensity CD38 expression was used to distinguish the plasma cell population and the cells were permeabilised to detect intracellular antigen expression. In situ hybridization using biotinylated cDNA probes for c-myc and bcl-2 was used to determine mRNA expression and to validate the flow cytometric assay. The normal range of expression for each of 6 oncoproteins (c-myc, c-fos, c-neu, bcl-2, p-ras, p53 mutant) and 2 tumour suppressor gene products (p53 wild and Rb) was determined in plasma cells from 33 normal bone marrows. Disease progression was associated with the concurrent abnormal expression of at least one oncogene and one tumour suppressor gene where as stable disease was associated with a normal expression of at least one or both (chi2 = 34.1; p < 0.001). At diagnosis there was a correlation between serum beta2 microglobulin and the concurrent overexpression of both an oncoprotein and a tumour suppressor gene product. Longitudinal studies of 33 different patients over 4 years, suggests that the progressive evolution of myeloma is a multistep process of genomic instability producing ongoing alterations in the expression of both oncogenes and tumour suppressor genes.
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PMID:Disease progression in patients with multiple myeloma is associated with a concurrent alteration in the expression of both oncogenes and tumour suppressor genes and can be monitored by the oncoprotein phenotype. 925 Aug 26

The malignant plasma cells from patients with multiple myeloma display considerable phenotypic heterogeneity. All plasma cells express high intensity CD38 (CD38++), cytoplasmic immunoglobulin and either kappa or lambda light chains. Subpopulations of mature (CD45-), immature (CD45+) and primitive (CD45++, CD19+) plasma cells can be defined but little is known about the functional differences and clinical significance of these subpopulations. Three colour flow cytometry and permeabilisation was used to determine the expression of functionally important antigens in plasma cell subpopulations. These antigens included the labelling index (LI, bromodeoxyuridine), number of nucleoside transporter per cell, p-glycoprotein (JSB-1), and oncoprotein expression (c-myc, c-fos, c-neu, bcl-2, p-ras, p53m, p-53w, and Rb). In progressive disease there was an increase in the absolute number but not the percentage of CD45++ plasma cells. There was a significant difference in the mean LI of the CD38++, CD45++ population in progressive disease compared with stable disease (9.2% vs 2.2%; z = 19.9, p < 0.001). The LI of CD45++ cells ranged up to 45% and provided a better correlation with disease status than the LI of the total cell population. Any increase in nucleoside transporters or p-glycoprotein expression was almost entirely attributable to an increase in the primitive plasma cell population. In 96% (n = 28) of samples from patients in progressive disease there was at least one abnormality in the functional phenotype of the primitive plasma cells. This is in contrast with 44% of samples from patients in stable disease (n = 58). These studies suggest that the functional phenotype of the primitive plasma cell determines the clinical phenotype of patients with myeloma.
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PMID:The functional phenotype of the primitive plasma cell in patients with multiple myeloma correlates with the clinical state. 937 99

We describe here a case of malignant lymphoma (ML) which coexpressed common acute lymphoblastic leukemia antigen (CALLA:CD10) and NRAS p21 and c-erbB-2 (neu) oncogene products. The patient, an 83 year-old man, had massive generalized lymphadenopathy and pleural effusions. Serum LDH levels were elevated to 801 IU/L. Surface phenotypes were analysed by a fluorescent-activated cell sorter with a panel of monoclonal antibodies (MAbs). The ML cells coexpressed antigens detected by MAbs CD10, CD19, CD20, CD22, CD24, CD38, Ia (HLA-DR), c-neu and surface immunoglobulin (Ig) G, Kappa. Gene rearrangements for the Ig JH and JK were found. Overexpression of NRAS p21 was shown by gene amplification using Southern blot analysis, while gene amplification of c-erbB-2 oncogene was also demonstrated. To our knowledge, this is the first report to demonstrate an overexpression of p185 c-neu on ML cells. These findings suggest that the p185 neu may be a prognostic indicator not only for breast adenocarcinomas but also for lymphoproliferative disorders, and that the transforming p185 protein may be involved in the mechanisms of aggressive expansion of lymphoid neoplasias.
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PMID:Aggressive Diffuse Lymphoma Coexpressing NRAS p21 and C-erbB-2 (neu) Oncogene Products, and CALL A (CD 10). 2746 77