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)

The tie gene encodes a receptor tyrosine kinase that together with its thus far unidentified ligand appears to play a distinct role in the regulatory pathway of early hematopoiesis and angiogenesis. Here, we attempted to define the possible involvement of tie in the pathobiology of hematopoietic malignancies by examining tie mRNA expression in human leukemia and lymphoma cells. We used a large panel of 93 well-characterized human continuous leukemia-lymphoma cell lines as model systems for the various hematopoietic cell lineages. At the Northern blot level, none of the 27 lymphoid leukemia or lymphoma-derived cell lines (originating from four B-precursor leukemia, four B-cell leukemia, four B-cell non-Hodgkin's lymphoma, two myeloma, two Burkitt lymphoma, four T-cell leukemia, five Hodgkin lymphoma, two anaplastic large cell lymphoma) tested expressed tie transcripts, whereas 23/42 (55%) of the myeloid cell lines analyzed expressed tie mRNA: in detail, 15 of 20 (75%) megakaryocytic, five of 11 (45%) erythroid, three of seven (43%) myelocytic and none of four monocytic cell lines were tie mRNA positive. In the reverse transcriptase-polymerase chain reaction analysis, which can detect very low levels of mRNA expression, all 12 myeloid cell lines and 19 of 39 (48%) lymphoid cell lines were positive. In experiments aimed at inducing cellular differentiation over an incubation period of 4 days, the phorbol ester PMA strongly enhanced tie mRNA expression in one erythroid and in one myelocytic cell line, but (like thrombopoietin) down-regulated tie mRNA expression in two megakaryocytic cell lines. Taken together these results indicate that tie is predominantly expressed in leukemia cells derived from the myeloid cell lineages (and here in particular in megakaryoblastic cells) and not in lymphoid leukemia cells. These observations provide some evidence for the hypothesis that tie is a receptor for a regulatory factor involved in normal and plausibly also leukemic hematopoiesis.
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PMID:Expression of tie receptor tyrosine kinase in human leukemia cell lines. 930 79

Homeobox (HOX) genes are involved in the lineage-specific differentiation of bone marrow stem cells. Recently, we reported a largely similar expression pattern of HOXC4 and HOXC6 in normal and neoplastic cells of the lymphoid lineage. In contrast, HOXC5 was specifically expressed in a subset of B-cell non-Hodgkin's lymphomas (B-NHL) but not in normal lymphocytes or lymphoid leukemias. This might suggest a role for HOXC5 in the pathogenesis of these lymphomas. In the present study the expression of HOXC4, HOXC5, and HOXC6 in primary cutaneous lymphomas was investigated. Using RNA in situ hybridization (RISH) and semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR), we found strong expression of HOXC4 and HOXC6 in all, except one, primary cutaneous lymphomas and all reactive cutaneous lymphoid infiltrates. Interestingly, a strong expression of HOXC5 in primary anaplastic CD30+ large T-cell lymphomas was found. RISH was consistently negative for HOXC5 in all other types of primary cutaneous B- and T-cell lymphomas. However, by semiquantitative RT-PCR these lymphomas showed a weak expression of HOXC5 mRNA. Therefore, we concluded that these lymphomas express low constitutive levels of HOXC5 mRNA. Furthermore, HOXC5 expression was consistently absent in reactive cutaneous lymphoid infiltrates, hyperplastic tonsils and lymph nodes, and peripheral blood lymphocytes either unstimulated or stimulated by a cocktail of CD3 and CD28 antibodies. As a strong expression of HOXC5 in primary cutaneous lymphomas was observed only in anaplastic large T-cell lymphomas and reactive control tissues lacked HOXC5 expression, these data strongly support a role for HOXC5 in the genesis of anaplastic large-T-cell lymphomas.
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PMID:HOXC4, HOXC5, and HOXC6 expression in primary cutaneous lymphoid lesions. High expression of HOXC5 in anaplastic large-cell lymphomas. 932 40

Fas ligand (FasL) is capable of inducing apoptosis of lymphoid cells by cross-linking with its natural receptor, Fas. We aimed to investigate the possible role of the Fas/FasL-mediated apoptosis in the development of human lymphomas. FasL mRNA was detected by reverse transcriptase-polymerase chain reaction in 38 out of 63 lymphoma biopsy specimens representative of various subtypes of non-Hodgkin's lymphoma (NHL) and Hodgkin's disease. FasL was co-expressed with Fas mRNA in most cases. Flow cytometry (FACS) analysis showed a bright FasL staining in 31% to up to 75% of the total cell population from 14 out of 16 samples; the presence of the FasL protein was confirmed by Western blotting. Dual-color FACS analysis showed that FasL was expressed by T cells in B-NHLs and T-NHLs. A significant percentage of B cells in various B-NHLs also stained positively for FasL. Freshly separated neoplastic B cells from three FasL+ and one FasL- B-NHLs displayed a relative resistance to Fas-mediated apoptosis, when compared to reactive T cells isolated from the same tissue samples. In contrast, the sensitivity to Fas-mediated killing of the T cells isolated from two FasL+ T-NHLs was not uniform. These data show that (1) FasL is expressed in both neoplastic and reactive cells from a significant proportion of lymphoma cases, and (2) that the intratumoral FasL+/Fas+ reactive T cells are more sensitive to Fas-induced apoptosis than the neoplastic FasL+/Fas+ malignant B cells. A putative defect in the Fas/FasL pathway may thus favor the development of malignant B cell populations.
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PMID:Malignant and reactive cells from human lymphomas frequently express Fas ligand but display a different sensitivity to Fas-mediated apoptosis. 936 20

Increasing evidence suggests that the hepatitis C virus (HCV) might be involved in the pathogenesis of B cell non-Hodgkin's lymphomas (NHL). Since several HCV genotypes are currently identifiable and might be involved in the pathogenesis of different diseases (with different severity and responsiveness to therapy), the aim of our study was to assess the prevalence of viral genotypes in a group of patients with HCV-related NHL. Among 470 consecutive patients, 42 HCV Ab-positive cases were identified. HCV RNA could be detected by reverse transcriptase-polymerase chain reaction and genotyping performed in 31 of these cases. As compared to our control group (211 healthy blood donors and patients with chronic liver disease), a striking high prevalence of genotype 2ac was detected among B cell NHL (48.4 vs 9.0%), with a relative risk of infection of 5.37 (P < 0.0001). No major differences were observed in the distribution of NHL histotypes and in the clinical features among patients with genotype 1b (the other most frequent genotype) or 2ac, a part from a trend towards a higher percentage of liver disease and a lower likelihood of response to interferon for patients with genotype 1b. The same high prevalence of genotype 2ac has been recently reported in patients with mixed cryoglobulinemia (MC), monoclonal gammopathies, B cell NHL complicating MC and autoimmune hepatitis. All these data taken together suggest that genotype 2ac might be involved in the pathogenesis of lymphoproliferative and autoimmune disorders.
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PMID:The genotype of the hepatitis C virus in patients with HCV-related B cell non-Hodgkin's lymphoma. 944 35

T(3;14)(q27;q32) is frequently detected in B-cell non-Hodgkin's lymphomas, especially the diffuse large cell type and the follicular type. The BCL6 gene encoding a putative transcriptional factor which resides on 3q27 rearranges to the immunoglobulin heavy chain (IgH) gene on 14q32 in this chromosomal translocation. The upstream regulatory region of the BCL6 gene is replaced by the IgH gene. Deregulation of the BCL6 gene may contribute to tumourigenesis of these diseases. The rearrangement between the IgH and BCL6 genes generates chimaeric transcripts in which the joining (J) region of the IgH gene fuses to exon 3 of the BCL6 gene. We established a method to detect these chimaeric transcripts by reverse transcriptase polymerase chain reaction (RT-PCR) using the consensus sequence of the J region and the sequence of exon 3 of the BCL6 gene as primers. Using the semi-nested RT-PCR method and a cell line carrying t(3;14)(q27;q32), we detected one lymphoma cell among 10,000 background cells. We detected these chimaeric transcripts in two out of 13 clinical samples by this method. This method can detect t(3;14)(q27;q32) easily, whereas this alteration is frequently overlooked by routine karyotype analysis. Since this technique is sensitive enough to detect a small number of lymphoma cells with this genetic abnormality, it could be employed to detect contaminating lymphoma cells in bone marrow and peripheral blood and minimal residual diseases.
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PMID:Detection of chimaeric transcripts of the immunoglobulin heavy chain and BCL6 genes by reverse-transcriptase polymerase chain reaction in B-cell non-Hodgkin's lymphomas. 950 30

Dendritic cells (DC) are specialist antigen presenting cells which capture antigens in the periphery, migrate centrally, and present the processed antigens in the context of major histocompatibility complex and appropriate co-stimulatory molecules to T lymphocytes for the initiation of an immune response. DEC-205 has been identified as a putative antigen-uptake receptor, which is expressed abundantly on mouse DC. The recently cloned mouse DEC-205 cDNA predicts a molecular structure which has a marked similarity to the macrophage mannose receptor. Using reverse transcriptase-polymerase chain reaction (RT-PCR) and cDNA library screening, we obtained the full coding region of human DEC-205 cDNA from the Hodgkin's disease-derived L428 cell line. The predicted protein structure is a type I transmembrane protein of 1722 amino acids consisting of a signal peptide, cysteine-rich domain, fibronectin type II domain, ten carbohydrate recognition-like domains, transmembrane domain, and a cytoplasmic tail. Human DEC-205 is 77% identical to the mouse protein with completely conserved cysteines. The DEC-205 gene (LY75) was mapped to chromosome band 2q24 by somatic cell hybrid panel analysis and fluorescent in situ hybridization. Northern blot analysis detected 7.8 and 9.5 kilobase DEC-205 transcripts in myeloid, B lymphoid, and Hodgkin's disease-derived cell lines. RT-PCR analysis indicated that immature blood DC contain a barely detectable amount of DEC-205 transcripts but these were markedly increased upon differentiation/activation.
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PMID:cDNA cloning of human DEC-205, a putative antigen-uptake receptor on dendritic cells. 955 50

A recurrent, reciprocal balanced translocation, t(2;5) (p23;q35), has been recognized in CD30+ anaplastic large-cell lymphomas (ALCL), a newly recognized subtype comprising approximately 5% of all non-Hodgkin's lymphoma (NHL). This translocation creates a novel fusion protein, NPM-ALK, which has transforming properties in vitro and can cause large-cell lymphoma in vivo when transfected into murine bone marrow. Multiple techniques including reverse transcriptase-polymerase chain reaction (RT-PCR) amplification of NPM-ALK fusion transcripts, genomic DNA-PCR, RNA in situ hybridization, and fluorescence in situ hybridization (FISH) of metaphase chromosomes and interphase nuclei, and immunohistochemical detection of the 80 kilodalton protein (p80) derived from the NPM-ALK fusion have enabled surveys of normal and lymphoma tissues for evidence of the translocation. These studies suggest that expression of ALK protein, a novel orphan receptor tyrosine kinase, is normally confined to the nervous system. In lymphoma, NPM-ALK expression is most often seen in young patients with the monomorphic or small-cell variant of ALCL who present with advanced stage disease and have tumors with a CD30+, T- or null-cell phenotype. It is less frequently detected in older patients and in ALCL of pleomorphic histology. In addition, expression of NPM-ALK has been found in occasional CD30 negative B-cell lymphomas with diffuse large cell or immunoblastic histology. NPM-ALK is rarely, if ever, detected in Hodgkin's disease or secondary ALCL. Although initially found in primary nodal ALCL, recent studies suggest that NPM-ALK expression may occur in lymphoma at extranodal sites, including the skin; it remains controversial, however, whether CD30+ primary cutaneous lymphoma and its benign counterpart, lymphomatoid papulosis (LyP), express NPM-ALK in some cases. A retrospective study has suggested that expression of NPM-ALK is associated with a better overall 5-year survival; these results must be confirmed in prospective studies of patients with uniform staging and therapy to more fully understand the clinical significance of the t(2;5) and its novel chimeric protein, NPM-ALK.
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PMID:The t(2;5) in human lymphomas. 968 23

Recent studies have shown that hepatocyte growth factor (HGF) is a regulatory protein for the proliferation and differentiation of hematopoietic progenitors. The proto-oncogene c-met encodes a tyrosine kinase receptor that binds HGF. To obtain information about their possible involvement in the pathogenesis of hematopoietic tumors, we have examined the expression of HGF and c-met in a large panel of leukemia-lymphoma cell lines encompassing all major hematopoietic cell lineages. HGF and c-met mRNAs were detected by reverse transcriptase-polymerase chain reaction (RT-PCR) and Northern blotting. The panel of 92 cell lines analyzed comprised seven B-cell precursor, ten B-cell, six plasma cell, 13 T-cell, four natural killer (NK) cell, 16 myelocytic, 12 monocytic, 13 erythroid-megakaryocytic and 11 Hodgkin-anaplastic large cell lymphoma (ALCL) lines. In total 64 (70%) were RT-PCR-positive for HGF and 43 (47%) for c-met. The highest percentages of expression were found for HGF in the plasma cell (100%), NK (100%) and myeloid (75-92%) cell line categories, whereas c-met was found predominantly in plasma cell (100%) and Hodgkin-ALCL (91%) cell lines. The concomitant expression of HGF and c-met in plasma cell lines (100%) and Hodgkin-ALCL (73%) cell lines should be noted. The high HGF expression in myelocytic-monocytic cell lines (75 and 92%) contrasts with the low c-met expression (18 and 8%) in these cell lineages. In 50 cell lines, mRNA expression of these two genes was also examined at the Northern blot level: 12/50 (24%) and 4/48 (8%) were positive for HGF and c-met mRNA expression, respectively. Of note, three of the four c-met + lines belonged to the category Hodgkin-ALCL; the Hodgkin cell line SUP-HD-1 showed both HGF and c-met mRNA bands suggesting the possibility of an autocrine loop. In conclusion, we detected HGF expression in various types of leukemia-lymphoma cell lines, particularly in plasma cell and myeloid malignancies; c-met expression was found in plasma cell and Hodgkin-ALCL cell lines. Further detailed analysis of the role of this ligand-receptor pair in the pathogenesis of hematopoietic neoplasms is indicated; to this end the HGF + and c-met + cell lines described here represent exquisite model systems.
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PMID:Expression of hepatocyte growth factor and its receptor c-met in human leukemia-lymphoma cell lines. 971 11

Nucleic acid sequence-based amplification (NASBA) assays were developed for direct detection of Epstein-Barr virus (EBV) transcripts encoding EBV nuclear antigen 1 (EBNA1), latent membrane proteins (LMP) 1 and 2, and BamHIA rightward frame 1 (BARF1) and for the noncoding EBV early RNA 1 (EBER1). The sensitivities of all NASBAs were at least 100 copies of specific in vitro-generated RNA. Furthermore, 1 EBV-positive JY cell in a background of 50,000 EBV-negative Ramos cells (the relative sensitivity) was detected by using the EBNA1, LMP1, and LMP2 NASBA assays. The relative sensitivity of the EBER1 NASBA was 100 EBV-positive cells, which was probably related to the loss of small RNA molecules during the isolation. The BARF1 and LMP2 NASBAs were evaluated on clinical material. BARF1 expression was found in 6 of 7 nasopharyngeal carcinomas (NPC) but in 0 of 22 Hodgkin's disease (HD) cases, whereas LMP2 expression was found in 7 of 7 NPCs and in 17 of 22 HD cases. For detection of EBNA1 transcripts in HLs (n = 12) and T- and B-cell non-Hodgkin's lymphomas (n = 3 and n = 2, respectively), NASBA was compared with reverse transcriptase (RT) PCR. Two samples were positive only with NASBA, and two other samples were positive only with RT-PCR; for all other samples, the RT-PCR and NASBA results were in agreement. We conclude that NASBA is suitable for sensitive and specific detection of the above-mentioned EBV transcripts, regardless of their splicing patterns and the presence of EBV DNA. The EBNA1, LMP2, and BARF1 NASBAs developed in this study proved to be reliable assays for detection of the corresponding transcripts in EBV-positive clinical material.
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PMID:Nucleic acid sequence-based amplification, a new method for analysis of spliced and unspliced Epstein-Barr virus latent transcripts, and its comparison with reverse transcriptase PCR. 977 58

Epstein-Barr virus (EBV) is a ubiquitous human herpesvirus which establishes life-long latency in the B-lymphocytes of infected individuals. Epstein-Barr virus is associated with Hodgkin's disease, AIDS-associated lymphoma and post-transplant lymphoproliferative disease (PTLD). In PTLD, the onset of malignancy correlates with a rise in EBV load. The relationship between malignancy and EBV load in other EBV-associated malignancies is not known. Epstein-Bar virus latency is associated with the expression of a limited set of viral transcripts. The most numerous of these are the EBERs (Epstein-Barr early RNAs). The high copy number of the EBERs in each latently infected cell led the author to combine serial dilution of lymphocytes with reverse transcriptase polymerase chain reaction (RT-PCR) for EBER-1 as a means to rapidly quantitate EBV load. The highest viral load was seen in a bone marrow transplant patient, where one in 3906 lymphocytes harboured EBV. Elevated viral load was seen in two solid-organ transplant patients. Viral loads in healthy volunteers ranged from less than one in 1x10(6) to one in 6.25x10(4). Reverse transcriptase polymerase chain reaction for EBER-1 in serial lymphocyte dilutions should allow the relationship of EBV load and malignancy to be examined in a number of disease settings and should also provide a quantitative picture of the impact of anti-viral therapy.
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PMID:Determination of Epstein-Barr virus (EBV) load by RT-PCR and cellular dilution. 984 61


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