Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019829 (Hodgkin's disease)
 30,247 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ltk is a new member of the ros/insulin receptor family of tyrosine kinases that is expressed in murine B-lymphocyte precursors and forebrain neurons. We previously reported that lymphoid ltk cDNAs predict a 69 kDa transmembrane glycoprotein, which uses a CUG translational start codon and has a 110 amino acid putative extracellular domain. We now show that the predominant ltk mRNA in brain is alternatively spliced and predicts a protein with a substantially larger extracellular part. The human ltk gene maps to chromosome 15, bands q13-21, a region containing the breakpoint of a recurring chromosomal abnormality in B-cell non-Hodgkin lymphomas.
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PMID:Alternatively spliced ltk mRNA in neurons predicts a receptor with a larger putative extracellular domain. 166 93

CD44 is a widely expressed, multifunctional, cell-surface glycoprotein that has been implicated in the regulation of normal hematopoiesis. In addition, expression of particular isoforms of CD44 has been associated with malignant transformation and/or the acquisition of metastatic potential. In this study, we used two recently developed monoclonal anti-CD44 antibodies, one reactive with an epitope shared by many CD44 isoforms and the other with an epitope unique to CD44 isoforms containing amino acids encoded by the alternatively spliced exon v10, to compare the expression of CD44 on primitive hematopoietic cells from the marrow of normal individuals and their neoplastic counterparts present in the peripheral blood of patients with chronic myeloid leukemia (CML). Multiparameter fluorescence-activated cell sorter (FACS) analysis and cell sorting studies showed that CD44 is normally expressed at high to very high levels on both long-term culture-initiating cells (LTC-IC) and granulopoietic colony-forming cells (granulocyte-macrophage colony-forming units [CFU-GM]). In contrast, primitive erythropoietic progenitors (burst-forming units-erythroid [BFU-E]) in normal marrow were more homogeneous in their expression of CD44, and very few (less than 5%) showed the very high levels of CD44 seen on 20% to 25% of LTC-IC and CFU-GM. Antibody staining showed the expression of exon v10-containing CD44 isoforms to be restricted to a small subpopulation (4% to 8%) of morphologically recognizable mature (CD34-) myeloid cells within the light-density fraction of normal marrow cells. Reverse transcription-polymerase chain reaction (RT-PCR) analysis showed the presence of two exon v10-containing mRNA species. In CML, a significantly greater proportion of the circulating neoplastic CFU-GM expressed very high levels of CD44, and these CFU-GM were accompanied by an increased number of light density v10+ cells, including some that coexpressed CD34. Nonmalignant hematopoietic progenitors mobilized by prior chemotherapy and growth factor treatment of patients with Hodgkin's disease or acute myeloid leukemia in remission showed no changes in CD44 expression relative to normal marrow progenitors. These results provide evidence of early differentiation-associated changes in CD44 expression during normal hematopoiesis in vivo that may be deregulated in the neoplastic clone of patients with CML.
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PMID:Differentiation-associated changes in CD44 isoform expression during normal hematopoiesis and their alteration in chronic myeloid leukemia. 757 90

The presence of soluble differentiation antigens has been recently shown in the sera of healthy subjects and in different pathological disorders. These soluble antigens represent truncated froms of membrane receptors that lack transmembrane and intracytoplasmic domains. They may rise from proteolytic cleavage of the original membrane-bound receptor or by synthesis from separate alternatively spliced mRNA's coding for soluble forms. Increased levels of soluble IL-2R, sCD8 were found in adult T cell leukemia, hairy cell leukemia Hodgkin's disease, non-Hodgkin's lymphoma and chronic lymphocytic leukemia. The presence of sCD30 was found in the above mentioned diseases except for hairy cell leukemia. Serum levels of sIL-2R, sCD8, sCD30 antigens correlated strictly with disease activity and results of treatment.
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PMID:[Circulating cell differentiation antigens as markers of activity in lymphoproliferative diseases]. 806 7

CD40 is a membrane glycoprotein expressed on normal and neoplastic B lymphocytes. Stimulation through CD40 regulates important cellular functions, but the effects depend on its membrane density. While extensive studies have characterized CD40 in non-Hodgkin lymphomas of immunocompetent individuals, little is known on the characteristics of this molecule in lymphomas arising in immunocompromised hosts. The aim of this study was to characterize the pattern of CD40 expression in an in vitro model constituted by AIDS small non-cleaved lymphoma (SNCCL) cell lines. The analysis of CD45 isoforms, a group of molecules alternatively spliced during B cell differentiation, has been chosen to correlate this process to the number of CD40 molecules per cell in these cell lines. Since Apo 1/Fas expression is upregulated on B lymphocytes after CD40 ligation and this expression is functionally relevant, we wanted to know whether a different CD40 pattern in AIDS-SNCCL cell lines could influence CD95 expression. We have shown that 3 of these cell lines (PA 682, Es III, and HBL-2) have high membrane CD40 expression (> 100,000 molecules/cell); they release large amounts of soluble CD40 (sCD40) in culture supernatants (>500 pg/ml), are CD45RA/RO double labelled, and express the Apo 1/Fas (CD95) antigen. On the contrary, low CD40 membrane antigen cell lines (BRGIgA, HBL-2, NC 71, AS 283A, and LAM C3+, < 50,000 molecules/cell) release low amounts of sCD40 (<300 pg/ml), are CD45RA+ but CD45RO-, and do not express CD95. EBV has no role in CD40 and CD45 isoform behaviour, because EBV superinfection of the EBV negative, low membrane CD40 HBL-2 cell line does not modify CD40 membrane expression, sCD40 production, or CD45 isoform and CD95 expression. Our data suggest that membrane CD40 in AIDS-SNCCL cell lines might be a key element in the regulation of their pathophysiology by influencing the expression of CD45 isoforms and of CD95, and by the release of its soluble form.
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PMID:High CD40 membrane expression in AIDS-related lymphoma B cell lines is associated with the CD45RA+, CD45RO+, CD95+ phenotype and high levels of its soluble form in culture supernatants. 905 40

We have studied the expression of the three human acute myeloid leukemia (AML) genes in primary samples of non-Hodgkin's B-cell lymphomas in which translocations involving these loci were not present. We found a widespread expression of the three AML genes in all the lymphoma samples as well as in the purified normal B-lymphocytes. Thus, the presence of the three mRNAs "per se" does not allow the identification of the pathological status. However, AML1 showed a different transcription pattern in the neoplastic tissues with respect to the normal B-cells. The AML1b isoform proved to be peculiar to this lymphoma. Our data support the idea that qualitative and quantitative alterations of AML1 gene expression deriving from deregulating mechanisms other than translocations may be involved in this malignancy. The usage of two differently regulated promoters driving the expression of the transcripts AML1b and AML1c may be one of these mechanisms. Finally, we report the presence of a new alternatively spliced transcript in normal B-cells.
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PMID:The expression pattern of the AML1 gene in non-Hodgkin's B-cell lymphomas and normal B lymphocytes. 1095 Sep 38

The development of human cancers is frequently associated with the silencing of the two major tumor suppressor pathways represented by retinoblastoma protein and p53. As the incidence of p53 mutations is significantly lower in Hodgkin's lymphoma than in other neoplasias, we investigated whether the malfunction of other proteins in this pathway could be responsible for its inactivation. Because the existence of nucleolar complexes between p14(ARF) and Hdm2 has been described as having a critical effect on p53 function by inhibiting its degradation, we analyzed the expression and subcellular localization of these proteins in 52 cases and in Hodgkin's cell lines. Two of four cell lines revealed loss of p14(ARF) expression secondary to gene promoter methylation, this being mutually exclusive with p53 mutations (1 of 4), illustrating the existence of selective pressure to inactivate the p53 pathway. The majority of Hodgkin's samples showed a strong nucleolar expression of p14(ARF) that was not associated with Hdm2. They also showed the existence of Hdm2/p53 complexes, and the absence of complexes containing either p14(ARF)/Hdm2 or p14(ARF)/p53. The different localization of Hdm2 (nucleoplasm) and p14(ARF) (nucleoli) observed in Hodgkin's tumors and cell lines is associated with the presence of short alternatively spliced transcripts of Hdm2 lacking the ARF-binding region and the nuclear export signal. The absence of these p14(ARF)/Hdm2 nucleolar complexes could be sufficient to inactivate the pathway and may explain the low frequency of p53 mutations in this tumor.
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PMID:Nucleolar p14(ARF) overexpression in Reed-Sternberg cells in Hodgkin's lymphoma: absence of p14(ARF)/Hdm2 complexes is associated with expression of alternatively spliced Hdm2 transcripts. 1183 77

Alternative splicing provides a versatile mechanism of gene regulation, which is often subverted in disease. We have used customized oligonucleotide microarrays to interrogate simultaneously the levels of expression of splicing factors and the patterns of alternative splicing of genes involved in tumor progression. Analysis of RNAs isolated from cell lines derived from Hodgkin lymphoma tumors indicate that the relative abundance of alternatively spliced isoforms correlates with transformation and tumor grade. Changes in expression of regulators were also detected, and a subset sample was confirmed at the protein level. Ectopic expression of neuron-specific splicing regulatory proteins of the Nova family was observed in some cell lines and tumor samples, correlating with expression of a neuron-specific mRNA isoform of JNK2 kinase. This microarray design can help assess the role of alternative splicing in a variety of biological and medical problems and potentially serve as a diagnostic tool.
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PMID:Alternative splicing microarrays reveal functional expression of neuron-specific regulators in Hodgkin lymphoma cells. 1554 66

The HDM2 oncoprotein is a cellular inhibitor of p53 and is frequently deregulated in human cancer. However, the HDM2 gene encodes alternatively spliced variants whose functional significance is poorly understood. We had previously reported the detection of alternative HDM2 forms in Hodgkin's lymphoma (HL)-derived cell lines. Here, we have cloned several of these transcripts, including the previously described HDM2-A, -B and -C (which encode the COOH terminus of HDM2), and two novel variants (HDM2-HL1 and -HL2) containing a complete p53 interaction domain. Real-time PCR assays demonstrated that HDM2-A and -B were selectively expressed by HL cell lines and primary tumors, compared with their non-neoplastic counterparts. In transient transfection experiments, alternatively spliced HDM2 isoforms were partially or totally localized within the cytoplasm. HDM2-HL2 was able to inhibit transactivation of a p53-inducible reporter construct and induced a partial relocalization of p53 to the cytoplasm. Expression of HDM2-A and -B caused the activation of p53/p21 and induced growth arrest in primary cells, but also increased the expression levels of cyclins D1 and E. Other possible genes regulated by HDM2-A and -B were identified using cDNA microarray technology. These results imply that HDM2 isoforms may have multiple effects on cell cycle control, and provide insight into the mechanisms through which these molecules contribute to tumorigenesis.
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PMID:Hodgkin's lymphoma cells express alternatively spliced forms of HDM2 with multiple effects on cell cycle control. 1633 Dec 55

The FOXP1 forkhead transcription factor is targeted by recurrent chromosome translocations in several subtypes of B-cell non-Hodgkin lymphomas, where high-level FOXP1 protein expression has been linked to a poor prognosis. Western blotting studies of diffuse large B-cell lymphoma (DLBCL) cell lines unexpectedly identified the atypical high-level expression of 2 smaller, 60 to 65 kDa, FOXP1 isoforms in all 5 of those with the activated B cell (ABC)-like DLBCL subtype and in a subgroup of primary DLBCL. The anti-FOXP1 (JC12) monoclonal antibody cannot distinguish FOXP1 isoforms by immunohistochemistry, a finding that may be clinically relevant as high-level expression of the full-length FOXP1 protein was observed in some germinal center-derived DLBCLs. ABC-like DLBCL-derived cell lines were observed to express 2 novel, alternatively spliced FOXP1 mRNA isoforms, encoding N-terminally truncated proteins. These transcripts and the smaller protein isoforms were induced as a consequence of normal B-cell activation, which thus represents an additional mechanism for up-regulating FOXP1 expression in lymphomas. The expression of potentially oncogenic smaller FOXP1 isoforms may resolve the previously contradictory findings that FOXP1 represents a favorable prognostic marker in breast cancer and an adverse risk factor in B-cell lymphomas.
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PMID:Potentially oncogenic B-cell activation-induced smaller isoforms of FOXP1 are highly expressed in the activated B cell-like subtype of DLBCL. 1807 90

Latent Epstein-Barr virus (EBV) infection is associated with several lymphoproliferative disorders, including posttransplant lymphoma, Hodgkin's disease, and Burkitt's lymphoma, as well as nasopharyngeal carcinoma (NPC). Twenty-nine microRNAs (miRNAs) have been identified that are transcribed during latent infection from three clusters in the EBV genome. Two of the three clusters of miRNAs are made from the BamHI A rightward transcripts (BARTs), a set of alternatively spliced transcripts that are highly abundant in NPC but have not been shown to produce a detectable protein. This study indicates that while the BART miRNAs are located in the first four introns of the transcripts, processing of the pre-miRNAs from the primary transcript occurs prior to completion of the splicing reaction. Additionally, production of the BART miRNAs correlates with accumulation of a spliced mRNA in which exon 1 is joined directly to exon 3, suggesting that this form of the transcript may favor production of miRNAs. Sequence variations and processing of pre-miRNAs to the mature form also may account for various differences in miRNA abundance. Importantly, residual intronic pieces that result from processing of the pre-miRNAs were detected in the nucleus. The predicted structures of these pieces suggest there is a bias or temporal pattern to the production of the individual pre-miRNAs. These findings indicate that multiple factors contribute to the production of the BART miRNAs and to the apparent differences in abundance between the individual miRNAs of the cluster.
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PMID:Epstein-Barr virus BART microRNAs are produced from a large intron prior to splicing. 1861 30


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