Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q06643 (non-Hodgkin's lymphoma)
 11,307 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Twenty-seven patients with non-Hodgkin's lymphoma (NHL) have undergone peripheral blood stem cell (PBSC) harvesting for autologous transplantation (Tx). A molecular marker was found at presentation in 23/27 patients. Immunoglobulin heavy chain (IgH) or T cell receptor beta (TCR beta) rearrangements were detected by Southern blotting or the polymerase chain reaction (PCR) in 13 patients; PCR detected the bcl-2/JH fusion in 10 patients. Fifteen autologous PBSC transplants have been performed in 11 patients. In 5/11 patients, the marker was present in at least one PBSC collection (in four patients, every PBSC collection was positive). Survival data are available for nine patients (two early deaths); three patients relapsed and died (221 - 930 d), one is alive and in relapse (354 + d) and five are alive and in complete remission (330 - 1290 + d). These findings suggest that tumour cell contamination of PBSC harvests is not uncommon. Whether these cells are clonogenic and contribute to disease relapse remains to be elucidated. The presence of residual disease at the time of transplantation and the reappearance (or persistence) of marker positive cells post-transplantation both appear to be poor prognostic factors for disease-free survival.
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PMID:Molecular detection of residual lymphoma cells in peripheral blood stem cell harvests and following autologous transplantation. 838 94

Molecular analysis of isolated single cells is a powerful tool for analyzing heterogeneity within a population of cells and for clarifying issues of cell origin and clonality. Current techniques are limited by the availability of suitable fresh tissue. To broaden the applicability of molecular techniques at single-cell level, we have developed an approach that uses routinely processed archival tissue. Immunoglobulin heavy chain (IgH) gene rearrangement was analyzed in large tumor cells from four cases of diffuse large cell B-non-Hodgkin's lymphoma and in small reactive T and B lymphocytes from three cases of lymphocytic predominance Hodgkin's disease. One case of Epstein-Barr virus (EBV)-encoded RNA (EBER)-positive angiocentric pulmonary T-cell lymphoma was assayed for the presence of the BamHI-W multiple-copy fragment of the EBV genome. T- and B-lymphoid cells were immunostained with anti-CD3 and CD20, respectively. The tissue sections from the EBER-positive T-cell lymphoma were stained by nonisotopic in situ hybridization. Single cells were mobilized after proteolytic treatment under an inverted microscope using a hydraulic micromanipulator at a magnification of 400 x. Isolated cells were aspirated into a micropipette fixed to a second micromanipulator and transferred into a PCR tube. The IgH complementarity determining region (CDR)3 was successfully amplified in 17 of 52 (33%) small B-lymphocytes from lymphocytic predominance Hodgkin's disease using a previously reported semi-nested PCR method, and the products from each case differed in size as expected of a polyclonal population. None of the 49 small T lymphocytes demonstrated any amplifiable IgH CDR3 products, indicating no significant cellular contamination. The IgH CDR3 sequence analysis of the PCR products indicated a clonal relationship among harvested cells. In the T-cell lymphoma case, the harvested EBER-positive cells were amplifiable for the multiple-copy fragment BamHI-W of the EBV genome. Our study indicates that single-cell analysis can be performed on paraffin-embedded archival tissue after being subjected to immunoperoxidase and in situ hybridization procedures.
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PMID:Molecular studies on single cells harvested by micromanipulation from archival tissue sections previously stained by immunohistochemistry or nonisotopic in situ hybridization. 904 58

Immunoglobulin heavy chain (IgH) gene rearrangement analysis was performed on 27 fine needle aspiration (FNA) specimens (13 reactive hyperplasia, 11 B cell non-Hodgkin's lymphoma (B-NHL), one Hodgkin's disease and two suspicious of non-Hodgkin's lymphoma). Satisfactory amplification was achieved in 23/27 cases. A polyclonal pattern was seen in 14 cases (11 reactive hyperplasia, one B-NHL, one suspicious of lymphoma, one Hodgkin's disease). A monoclonal band was seen in nine cases (eight B-NHL, one reactive hyperplasia). Amplification was unsuccessful in four cases. Clonal analysis by PCR-based IgH gene rearrangement analysis can be successfully applied to FNA material and can be useful in diagnosis, but the results must be interpreted in conjunction with morphology and other ancillary information.
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PMID:Analysis of clonality in cytologic material using the polymerase chain reaction (PCR). 913 37

Approximately 15% of all cases of childhood classical Hodgkin's disease (HD) express CD20, a B-cell marker associated with immunoglobulin heavy chain rearrangements. Immunoglobulin heavy chain rearrangements in Reed-Sternberg cells could be used to assess minimal residual disease (MRD), as was shown with immunoglobulin heavy chain patient-specific primers (PSPs) in non-Hodgkin's lymphoma. The aim of this study was to analyze pediatric HD for future design of immunoglobulin heavy chain PSP for MRD detection. DNA was extracted from paraffin-embedded tissue from unstained slides of 8 pediatric CD20+ nodular sclerosis HD cases and 10 CD20-nodular sclerosis HD cases. Immunoglobulin heavy chain polymerase chain reaction and sequencing were performed on 16 of 18 cases, which had adequate DNA for further analysis. Sequence analysis from 3 cases (19% of HD cases) demonstrated unique V(D)J regions, which could potentially be used to design PSP. Unique PSPs could be used to assess MRD in advanced-stage HD specimens. Future studies should focus on improved detection and analysis of more cases to identify appropriate specimens in assessing clinical implications of MRD detection.
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PMID:Assessing immunoglobulin heavy chain rearrangements in pediatric CD20-positive and CD20-negative classic Hodgkin's disease. 1563 94

Immunoglobulin heavy chain (IgH) translocations are common and early oncogenic events in B cell and plasma cell malignancies including B cell non-Hodgkin's lymphoma (NHL) and multiple myeloma (MM). IgH translocations bring oncogenes into close proximity with potent enhancer elements within the IgH locus, leading to oncogene up-regulation. As IgH enhancer activity is tightly controlled by B cell lineage-specific signaling and transcriptional networks, we hypothesized that IgH enhancers are potentially druggable targets/elements. To test this, we developed a molecular imaging-based high-throughput screening platform for discovering inhibitors of IgH enhancer-driven transcriptional activity. As proof of concept, we identified a low micromolar potency molecule (compound 30666) that inhibited immunoglobulin production by MM cells and blocked expression of an array of IgH translocation-induced oncogenes (CCND1, FGFR3/MMSET, and MYC) in MM and NHL cell lines. Prolonged exposure to 30666 significantly reduced the viability of IgH translocation-positive NHL and MM cells, but was less effective against cells lacking IgH translocations. Compound 30666 exhibited suitable pharmacological properties, including metabolic stability in liver microsomes and oral bioavailability in mice, and demonstrated preclinical anti-MM activity in a plasmacytoma mouse model. Our work suggests that IgH enhancers are attractive and potentially druggable targets for IgH translocation driven malignancies.
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PMID:Discovery platform for inhibitors of IgH gene enhancer activity. 3048 Nov 17