Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0079731 (B-cell lymphoma)
 16,671 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Immunoglobulin idiotypes (Id) of malignant B cells represent highly specific markers which can be used for vaccination. PCR-amplification of immunoglobulin genes enables the rapid production of large amounts of Id vaccines. However, the separate amplification and subsequent recombination of heavy and light chains can lead to a loss of the relevant Id. To preserve the original chain pairs, we used single malignant B cells derived from an immunocytoma patient. Cytoplasm was extracted and the mRNA transcribed into cDNA. The VH and VL genes were then amplified by PCR and cloned into a vector for expression in E. coli. Id production was checked using an anti-Id mouse monoclonal Ab raised against the patient's tumor-specific IgG. One out of 3 constructs expressed the relevant Id. Analysis of the first 31 light chain residues revealed an identical sequence for the malignant B cells' IgG and the recombinant Id construct. Exchange of either the heavy or light chain with an unrelated chain resulted in loss of the Id. An unrelated sequence derived from the c-myc protein is coupled to the Id vaccine. The lymphoma patient was shown to have Abs to the c-myc sequence. This sequence therefore, increases the Id+ Ab's antigenicity. CD spectroscopy showed an alpha-helical structure for the c-myc epitope. In conclusion, a B-cell lymphoma autovaccine was produced containing immunogenic sequences that do not alter the steric conformation of the tumor-specific Id.
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PMID:Idiotypic vaccine for treatment of human B-cell lymphoma. Construction of IgG variable regions from single malignant B cells. 945 90

The RCK gene was cloned through a study of the breakpoint of the t(11;14)(q23;q32) chromosomal translocation observed in a human B-cell lymphoma and overexpression of the protein (rck/p54) due to the translocation was shown to be associated with malignant transformation. The rck/p54 protein belongs to the DEAD box protein/RNA helicase family, which has a variety of functions such as translation initiation, pre-mRNA splicing and ribosome assembly. It is considered that rck/p54 protein may have significant effects on the mRNA structure of genes associated with cell proliferation, facilitating protein synthesis. Expression of rck/p54 in colorectal adenomas, which are a premalignant lesion of colorectal cancer, was examined by Western blot analysis and immunohistochemistry. The rck/p54 protein was found to be overexpressed in tumor tissues resected from 17 of 26 cases (65.4%) of colorectal adenomas and 13 of 14 c-myc-positive cases (92.8%) also co-overexpressed rck/p54 protein. Thus, a significant correlation between rck/p54 and c-myc co-overexpression was found (Spearman's rank correlation, P = 0.0018). We demonstrate that overexpression of rck/p54 in two different cell lines, COS 7 and human colorectal cancer cell line SW480, caused an increase in c-myc protein levels by enhancement of its translation efficiency and/or stabilization of its mRNA. These results suggest that rck/p54 of the DEAD box protein/RNA helicase family may contribute to cell proliferation and carcinogenesis in the development of human colorectal tumors at the translational level by increasing synthesis of c-myc protein.
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PMID:Co-overexpression of DEAD box protein rck/p54 and c-myc protein in human colorectal adenomas and the relevance of their expression in cultured cell lines. 1175 26

Translocations involving chromosome 8 are the most common aberrations in B-cell non-Hodgkin lymphoma (B-NHL). The presence of the typical t(8;14)(q24;q32) or its variants has been confirmed in all cases of Burkitt lymphoma (BL), in some cases of Burkitt-like lymphoma (BLL), and in diffuse large B-cell lymphoma (DLBCL). The alterations lead to deregulated expression of c-myc protein by a chromosomal translocation joining C-MYC gene with sequences from immunoglobulin (Ig) enhancers. The C-MYC gene rearrangement plays an essential role in leukemogenesis of BL and probably plays a part in other aggressive NHLs. The present study was undertaken to compare the cytogenetic features in cases of BL, BLL, and DLBCL. We detected chromosomal aberrations by G-banding and fluorescence in situ hybridization (FISH) painting in 10 cases of aggressive B-NHL and used FISH to visualize the C-MYC gene rearrangement. Chromosome 8 was most frequently involved in structural aberrations (8/10 cases), and 4 cases showed the typical t(8;14)(q24;q32). Only two of 5 patients suspected of having BL fulfilled all the criteria for this diagnosis; in the others, chromosome 8 was aberrant, but the absence of C-MYC rearrangement or the results of flow cytometry excluded the diagnosis of BL. All BLL cases showed C-MYC overexpression, but only one had a rearrangement of the C-MYC gene; the remaining cases showed other aberrations of chromosome 8. This study indicates that the mechanisms of C-MYC activation involved in BLL can be different from that for the BL.
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PMID:Frequent aberrations of chromosome 8 in aggressive B-cell non-Hodgkin lymphoma. 1564 90

Interleukin-4 (IL-4) promotes lymphocyte survival and protects primary lymphomas from apoptosis. Previous studies reported differential requirements for the signal transducer and activator of transcription 6 (STAT6) and IRS2/phosphatidylinositol 3 kinase (PI-3K) signaling pathways in mediating the IL-4-induced protection from Fas-mediated apoptosis. In this study, we characterized IL-4-activated signals that suppress anti-IgM-mediated apoptosis and growth arrest of CH31, a model B-cell lymphoma line. In CH31, anti-IgM treatment leads to the loss of mitochondrial membrane potential, phospho-Akt, phospho-CDK2, and c-myc protein. These losses are followed by massive induction of p27(Kip1) protein expression, cell cycle arrest, and apoptosis. Strikingly, IL-4 treatment prevented or reversed these changes. Furthermore, IL-4 suppressed the activation of caspases 9 and 3, and, in contrast to previous reports, induced the phosphorylation (deactivation) of BAD. IL-4 treatment also induced expression of BclxL, a STAT6-dependent gene. Pharmacologic inhibitors and dominant inhibitory forms of PI-3K and Akt abrogated the anti-apoptotic function of IL-4. These results suggest that the IL-4 receptor activates several signaling pathways, with the Akt pathway playing a major role in suppression of the apoptotic program activated by anti-IgM.
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PMID:IL-4 protects the B-cell lymphoma cell line CH31 from anti-IgM-induced growth arrest and apoptosis: contribution of the PI-3 kinase/AKT pathway. 1796 25

Nearly 100% of Burkitt lymphomas (BLs) and 5% to 8% of diffuse large B-cell lymphomas (DLBCLs) harbor a balanced translocation involving c-MYC. Although characteristic morphologic and immunophenotypic features can identify BL in most cases, tumors with atypical features are often encountered in clinical practice. Furthermore, no morphologic or immunophenotypic finding can predict an underlying c-MYC translocation in DLBCL with certainty. Here we report on a novel monoclonal antibody recognizing the c-myc protein in formalin-fixed, paraffin-embedded tissue which we used to evaluate a spectrum of aggressive B-cell lymphomas by standard immunohistochemistry. Cases consisted of 17 BLs (15 cases with confirmed c-MYC translocation), 19 DLBCLs without a c-MYC translocation, 5 DLBCLs with a c-MYC translocation, and 2 B-cell lymphomas, unclassifiable, with features intermediate between DLBCL and BL (intermediate DBLCL/BL, one case with c-MYC translocation and one case without a c-MYC translocation). The intensity and subcellular localization of tumor-specific staining for c-myc protein was determined independently by 2 pathologists and in a blinded fashion for each case. We observed c-myc expression in the tumor cells of all cases regardless of c-MYC status. Among BLs, c-myc protein primarily localized to the nucleus of tumor cells in 15 of 17 cases (88%) and equally localized to the nucleus and cytoplasm of tumor cells in 2 of 17 cases (12%). In no case did c-myc protein primarily localize to the cytoplasm. In contrast, among DLBCLs lacking a c-MYC translocation the c-myc protein primarily localized to the cytoplasm of the tumor cells in 18 of 19 cases (95%) and equally localized to the nucleus and cytoplasm in the tumor cells in 1 of 19 cases (5%). In no case did c-myc protein primarily localize to the nucleus. Among DLBCLs with a c-MYC translocation and intermediate DBLCL/BLs, the c-myc protein primarily localized to the nucleus, or equally localized to the nucleus and cytoplasm of the tumor cells in 4 of 5 cases (80%) and 2 of 2 cases (100%), respectively. Taken together, we find that a primarily nuclear or mixed nuclear and cytoplasmic staining pattern for c-myc in an aggressive B-cell lymphoma is highly predictive of a c-MYC translocation (positive-predictive value=0.92, negative-predictive value=0.95, P<0.0001). We further show that the subcellular localization of c-myc can be determined with good interobserver agreement among pathologists (kappa statistic=0.90). Thus this novel immunohistochemsitry test is a useful tool for identifying aggressive B-cell lymphomas likely to harbor a c-MYC rearrangement and thus warrant genetic testing.
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PMID:Altered subcellular localization of c-Myc protein identifies aggressive B-cell lymphomas harboring a c-MYC translocation. 2044 43