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 present study analyzes the efficiency of a combination of four immunoglobulin heavy chain (IgH) gene polymerase chain reaction (PCR) primer systems and a multiplex T-cell receptor gamma chain (TRG) gene PCR for detection of clonality in 409 samples (234 paraffin sections, 175 bone marrow aspirates) of different lymphomas. Using the four IgH PCR systems together, clonality was detected in all samples of B-cell chronic lymphocytic leukemias, hairy cell leukemias, common acute lymphoblastic leukemias, and Burkitt-like B-cell lymphomas. Clonality was detected in all bone marrow aspirates with lymphoplasmacytoid immunocytoma, mantle cell lymphoma, marginal zone B-cell lymphoma, and unclassifiable low-grade B-cell lymphomas. The combined IgH gene PCR approach allowed clonality detection in 78.2% of myelomas, 75% of Burkitt lymphomas, 74.4% of diffuse large B-cell lymphomas, 68.7% of follicular center lymphomas, 50% of posttransplant lymphomas, 28.6% of anaplastic large cell lymphomas, 29% of T-cell lymphomas, and 18.8% of Hodgkin diseases. The combination of the four IgH gene primer systems with the multiplex TRG gene PCR allowed detection of clonality in 84.2% of B-cell neoplasms, 92.1% of T-cell non-Hodgkin lymphomas, and 18.8% of Hodgkin diseases, which was much more efficient than single PCR protocols.
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PMID:Combined polymerase chain reaction approach for clonality detection in lymphoid neoplasms. 1047 82

Apoptosis is a physiological process wherein the cell initiates a sequence of events culminating in the fragmentation of its DNA, nuclear collapse, and finally disintegration of the cell into small, membrane-bound apoptotic bodies. Expression of Fas (APO-1, CD95) Receptor (FasR) and programmed or active cell (PCD) death was studied in childhood astrocytomas (ASTRs) with varying stages of malignancy, including pilocytic ASTR, low grade ASTR, anaplastic ASTR, and glioblastoma multiforme (GBM). The great majority of childhood glial tumors, particularly ASTRs express FasR whereas normal cells in the central nervous system (CNS) do not. FasR represents a transmembrane glycoprotein which belongs to the nerve growth factor/tumor necrosis factor (NGF/TNF) receptor superfamily. Apoptosis within ASTRs is triggered by the binding of FasR to its natural ligand (FasL) or by cross-linking with antibodies developed against FasR. Presence of FasL was also detected in childhood glial tumors. The expression of both FasR and FasL was also observed within the same ASTRs. Therefore, spontaneous, IP regulatory, intratumoral apoptotic cell death (autocrine suicide) is possible in childhood glial tumors. During a systematic, immunocytochemical screening of 42 childhood ASTRs tissues divided according to WHO classification: 6 WHO grade I or pilocytic ASTRs; 14 WHO grade II or low grade ASTRs; 16 WHO grade III or anaplastic ASTRs and 6 WHO grade IV or glioblastoma multiforme (GBM), we detected strong expression (intensity of staining: "A"--the highest possible; number of stained cells: +2 to +4, between 20% to 90%) of FasR, employing 4 microns thick, formalin fixed, paraffin-wax embedded tissue slides. FasR was present on 70% to 90% of tumor cells in pilocytic ASTRs, in 50% to 60% of the tumor cells in low grade ASTRs, in between 30% and 40% of the tumor cells in anaplastic ASTRs, and in between 20% to 35% of GBM cells. The panel of normal tissues employed as positive and negative tissue controls demonstrated presence of FasR in the prenatal thymus, mature tonsils and colonic epithelium. The use of a sensitive, indirect, six step immunoperoxidase or alkaline phosphatase conjugated streptavidin-biotin antigen detection technique provided excellent immunocytochemical results. A broad spectrum of neoplastic cells have been identified to express FasR: 1) carcinomas of epithelial origin, such as breast (ductal invasive, lobular invasive, mucinous), renal cell, gastric, colorectal, endometrial, prostate, pancreas, hepatocellular and large cell and squamous cell lung carcinomas: 2) non-epithelial neoplasms such as B cell mediastinal B cell and nodal non-Hodgkin's lymphomas large granular lymphocytic leukemia of T or NK cell origin malignant fibrous histiocytoma, malignant mesothelioma, leiomyosarcoma, epitheloid sarcoma and alveolar soft part sarcoma, as well as melanomas. Flow cytometry studies have also detected FasR expression on cells of adult T cell, and hairy cell leukemias, as well as in chronic B cell lymphocytic leukemia (BCLL). The coexpression of both FasR and FasL on several malignant cell types may represent an effective mechanism of tumor escape from the cellular immunological response of the host. It has been well established that brain tumors and melanomas produce their autocrine FasL, and even become capable of switching the signal transduction associated with FasL-FasR coupling from the PCD pathway to a tumor growth, proliferative pathway. It seems that the therapeutical use of FasR-FasL (main apoptotic pathway) may represent a new and exciting type of immunotherapy in the treatment of primary childhood glial tumors.
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PMID:Fas (Apo-1, CD95) receptor expression in childhood astrocytomas. Is it a marker of the major apoptotic pathway or a signaling receptor for immune escape of neoplastic cells? 1058 78

This study analyzed the expression of the beta2 integrin CD11c in 155 patients with well-characterized B-cell chronic lymphoproliferative disorders: 106 B-cell chronic lymphocytic leukemias (B-CLL), 21 hairy cell leukemias (HCL), 9 B-cell prolymphocytic leukemias (PLL) and 19 low grade non-Hodgkin's lymphomas (NHL) in leukemic phase. CD11c was expressed in 100% of patients with HCL and B-PLL, while in B-CLL and NHL it was expressed in only 49 and 57%, respectively. Furthermore, in B-CLL the expression of CD11c was found mainly in patients with early stage of disease. In addition, when the fluorescence intensity of CD11c, calculated by MFI, was evaluated, it proved significantly higher in HCL and B-PLL compared to the values recorded in B-CLL and NHL (325 and 387 vs 34 and 56, respectively) (p < 0.05). Our results demonstrate that the evaluation of CD11c, both in terms of overall positivity and of fluorescence intensity, represents an additional useful parameter for a more precise differential diagnosis within the spectrum of B-cell chronic lymphoproliferative disorders.
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PMID:Expression of the CD11c antigen in B-cell chronic lymphoproliferative disorders. 1072 78

Similar to the R.E.A.L-System, the small cell B-cell lymphomas of the new WHO classification consist of chronic lymphocytic leukaemia of B cell type, mantle cell lymphoma, follicular lymphoma, lymphoplasmocytic lymphoma/immunocytoma, hairy cell leukaemia, as well as plasmacytoma. The only major difference between the WHO- and the REAL-classification is the consideration of prolymphocytic leukaemia as a single disease entity in the former system. All the above-mentioned lymphomas arise from B cells of varying stages of differentiation and, therefore, often demonstrate architectural, cytological and immunophenotypic characteristics of their normal physiological counterparts. Consideration of tumour cell growth pattern, -cytology, -immunophenotype and -growth fraction, together with the presence and consistency of the reactive cell infiltrate, usually leads to categorisation of a lymphoma in the majority of cases. The molecular biological characteristics of follicular lymphoma and mantle cell lymphoma are the best defined of the small cell B-cell lymphomas. Chromosomal translocations involving the immunoglobulin heavy chain genes and the bcl-2 gene or Cyclin D1 gene, respectively, probably belong to the initial changes in a cell, which, together with several subsequent unidentified genetic alterations, lead to the development of these tumours. Although nodal small cell B-cell lymphomas are usually diagnosed at an advanced stage of the disease, the progression of the disease--with the exception of mantle cell lymphomas--is often indolent. As a result, the small cell B-cell lymphomas were previously considered as "low-grade" Non-Hodgkin lymphomas in the Kiel classification. However, since the progress of a lymphoma subtype can be heterogeneous and since mantle cell lymphomas cannot really be considered as "low-grade" tumours, "umbrella grading" of lymphomas has been discarded in the WHO classification, with emphasis being placed on grading within a lymphoma disease entity. In the following pages, the characteristics important for the diagnosis and categorisation of the small cell B-cell lymphomas will be summarised. Further, we present information regarding the molecular biological and clinical characteristics of these lymphomas.
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PMID:[Small cell B-cell lymphomas: guidelines for differential diagnosis]. 1084 Aug 20

The translocation (11;14)(q13;q32) and its molecular counterpart the BCL-1 rearrangement are features observed in mantle cell lymphoma (MCL) and less commonly in other B-cell disorders. This rearrangement leads to cyclin D1 overexpression, which may be the main pathogenic event in these tumours and is therefore recognised as a diagnostic marker. We developed a flow cytometry method to detect cyclin D1 overexpression using the monoclonal antibody (MoAb) 5D4, and characterised its frequency in 93 B-cell malignancies. The competitive reverse transcriptase polymerase chain reaction (RT-PCR) for cyclin D1, D2 and D3 was then performed on 40 of these cases to assess the validity of the flow cytometry method. Fluorescence in situ hybridisation (FISH) to detect t(11;14)(q13;q32) was carried out on 31 cases and results were compared with cyclin D1 expression by flow cytometry. Twenty five cases showed cyclin D1 expression using 5D4, including MCL (12/13, 92%), chronic lymphocytic leukaemia (CLL) (4/30), B-prolymphocytic leukaemia (B-PLL) (1/4), splenic lymphoma with villous lymphocytes (SLVL) (4/13), hairy cell leukaemia (HCL) (1/7) and other B-non Hodgkins Lymphoma (B-NHL) (3/15). There was a good correlation between flow cytometry results and RT-PCR in 36/40 cases (90%), and with FISH for t(11;14) in 25/31 cases (80%). We concluded that the detection of cyclin D1 expression by flow cytometry in cell suspensions could be applied routinely to the study of B-lymphoproliferative disorders and may be of value for their diagnosis and management.
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PMID:Cyclin D1 by flow cytometry as a useful tool in the diagnosis of B-cell malignancies. 1116 26

Chemokines are a family of 8-10 kDa proteins with a wide range of biological activities including the regulation of leukocyte trafficking, modulation of haemopoietic cell proliferation and adhesion to extracellular matrix molecules. Using a panel of chemokine receptor-specific monoclonal antibodies (MoAb) in a multicolour flow cytometry approach we analysed the expression of the lymphocyte-associated chemokine receptors CXCR4, CXCR5, CCR5 and CCR6 in B cell acute lymphoblastic leukaemia (precursor B-ALL; six cases), B cell chronic lymphocytic leukaemia (B-CLL; 31 cases), multiple myeloma (10 cases), mantle cell lymphoma (MCL, four cases), follicular lymphoma (FL, three cases) and hairy cell leukaemia (HCL, five cases). We demonstrate that CXCR4, CXCR5 and CCR6 are differentially expressed in these B lymphoproliferative disorders depending on the maturational stage of the malignant B cell population investigated. In particular, we found that CXCR4 is strongly expressed on immature ALL blasts whereas no surface immunoreactivity for CXCR5, CCR5 and CCR6 was observed. By contrast, non-Hodgkin's lymphomas (NHLs) corresponding to more mature peripheral B cell subsets (ie B-CLL and MCL) exhibited high expression levels of CXCR4 and CXCR5. Analysis of terminally differentiated myeloma cells revealed a down-regulation of CXCR4, CXCR5 and CCR6. CCR5, which is not expressed in normal B cells, was also absent from the majority of NHLs. However, CCR5 staining was seen in three of five cases of HCL, representing the first example of cross-lineage aberrant chemokine receptor expression in malignant haemopoietic cells.
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PMID:Differential expression of chemokine receptors in B cell malignancies. 1136 35

SWAP-70 is a recently discovered member of the Dbl (diffuse B-cell lymphoma) family of signal transduction molecules that is abundantly expressed in B cells. SWAP-70 mediates lipid second-messenger signals to the cytoskeletal-organizing GTPase Rac, functioning as a guanine-nucleotide exchange factor. SWAP-70 is strongly expressed in germinal center B cells, with low-level expression in resting B-cells. Expression of SWAP-70 in neoplastic B cells has not been described. We report the immunohistochemical expression of SWAP-70 in 86 B-cell neoplasms. SWAP-70 was strongly expressed in 59 of the 86 cases: 2 of 10 (20%) precursor B-cell lymphoblastic leukemias, 2 of 2 (100%) precursor B-cell lymphoblastic lymphomas, 2 of 4 (50%) mantle cell lymphomas, 7 of 9 (78%) Burkitt lymphomas, 9 of 9 (100%) diffuse large B-cell lymphomas, 8 of 8 (100%) follicular lymphomas, 6 of 6 (100%) nodular lymphocyte predominant Hodgkin lymphomas, 0 of 8 (0%) classic Hodgkin lymphomas, 12 of 13 (92%) chronic lymphocytic leukemias, 3 of 3 (100%) nodal marginal zone lymphomas, 5 of 5 (100%) extranodal marginal zone lymphomas, 1 of 2 (50%) splenic marginal zone lymphomas, 2 of 3 (66%) hairy cell leukemias, and 0 of 4 (0%) plasma cell neoplasms. All 4 T-cell lymphomas were nonreactive for SWAP-70: 0 of 3 peripheral T-cell lymphomas and 0 of 1 anaplastic large cell lymphoma. These results suggest that a spectrum of neoplastic B cells maintains activation of this signal transduction pathway. This is the first report of the expression of a Dbl family molecule in human lymphoma and leukemia tissues.
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PMID:Expression of the diffuse B-cell lymphoma family molecule SWAP-70 in human B-cell neoplasms: immunohistochemical study of 86 cases. 1516 14

The recent approval of rituximab, gemtuzumab ozogamicin, alemtuzumab and ibritumomab tiuxetan by the FDA in the US revealed clear evidence that monoclonal antibodies (mAbs) have significant roles in the current treatment of haematologic malignancies. Among the mAbs under clinical development, anti-CD20 mAbs have been most extensively investigated and have shown definitive clinical efficacy. Rituximab is a genetically engineered chimeric anti-CD20 mAb, with mouse variable and human constant regions. Consecutive clinical trials conducted in the US, Europe and Japan have revealed that rituximab is a highly effective agent with acceptable toxicities against indolent and aggressive B cell non-Hodgkin's lymphomas (B-NHLs) as a single agent and in combination with cytotoxic drugs. A recent French Phase III study in elderly patients with untreated aggressive B-NHL suggested that the addition of rituximab to standard CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) chemotherapy increases the complete response rate and prolongs event-free and overall survival. Lymphoma cells are inherently sensitive to radiation. The aim of radioimmunotherapy is to use the mAb to target radiation to lymphoma tissue while minimising toxicity to normal cells. The clinical trials of 90Y ibritumomab tiuxetan and (131)I tositumomab showed they have definitive efficacy in relapsed indolent B-NHL with acceptable toxicities. A recent comparative study in relapsed indolent B-NHL showed that 90Y ibritumomab tiuxetan produces higher response rates than rituximab. In addition, BL22, a recombinant anti-CD22 immunotoxin, showed significant efficacy in patients with chemotherapy-resistant hairy cell leukaemia. MAbs will have significant roles in the treatment of lymphoid malignancies in the future.
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PMID:Rituximab and other emerging monoclonal antibody therapies for lymphoma. 1598 52

Cytogenetic analysis is now a routine part of the diagnosis and management of a significant number of lymphoid malignancies. Whilst conventional cytogenetics remains the most comprehensive method for assessing chromosome abnormalities, the technical difficulties associated with conventional cytogenetics in most lymphomas has resulted in increased use of fluorescence in situ hybridisation (FISH) to identify specific abnormalities that are useful in either the diagnosis or management of these disorders. The finding of one of the Burkitt's translocations is of major importance in the diagnosis of Burkitt's and Burkitt's-like lymphomas, whereas the t(14;18), although seen in most follicular lymphomas (FL), is not usually required to make a diagnosis. Thus, whilst cytogenetics may be of interest in FL, it is not an essential part of the diagnostic work-up. Conventional cytogenetics may be useful for identifying markers of resistance to Helicobacter pylori therapy in MALT lymphomas. In disorders such as Hodgkin lymphoma, hairy cell leukaemia and lymphoplasmacytoid lymphoma, although many cytogenetic abnormalities have been observed, no consistent or specific abnormalities have been identified and so, at this point in our knowledge of the genetics of these disorders, cytogenetics cannot be considered a useful test for either diagnosis or prognosis. In contrast, the diagnosis of mantle cell lymphoma is now dependent upon the identification of the 11;14 translocation that results in cyclin D1 up-regulation. It is widely acknowledged that FISH is the most consistently useful test to identify the juxtaposition of the CCND1 and IGH genes in mantle cell lymphoma and is regarded as the 'gold standard'. FISH also has a role in identifying genetic abnormalities of prognostic significance in chronic lymphocytic leukaemia. Given the wealth of genetic and cytogenetic abnormalities that are continuing to be found in chronic lymphoid malignancies, it will be some time before the optimal use of both conventional cytogenetics and FISH is established in the diagnosis and management of lymphomas.
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PMID:Cytogenetics of lymphomas. 1637 29

CD45 is a glycoprotein expressed in all lymphohemopoietic cells. Its expression increases during B-lymphocyte ontogeny. Few data are available about CD45 expression in the various types of low-grade B-cell non-Hodgkin's lymphomas (NHL). Low levels of CD45 have been reported in pathologic lymphocytes from typical chronic lymphocytic leukemia (CLL) and higher levels of this antigen have been observed in some cases of atypical CLL and in some cases of other types of NHL. One hundred and seven bone marrow samples of NHL with bone marrow infiltration were investigated: 45 typical CLL, 15 atypical CLL, 9 mantle cell lymphomas (MCL), 1 MCL with CD23 expression, 18 marginal zone lymphomas (MZL), 6 lymphoplasmacytic lymphomas (LPL), 6 follicular lymphomas (FL), and 7 hairy cell leukemias (HCL). CD45 expression was evaluated by flow cytometry: pathologic lymphocytes were identified on the basis of specific immunophenotypic profile, CD19/K or CD19/lambda co-expression. Results were expressed as median fluorescence intensity (MFI) along a 1024 linear scale. CD45 expression was measured also on autologous T-lymphocytes and a "CD45 index" was calculated as the ratio MFI of pathologic B-lymphocytes/MFI of T-lymphocytes, to normalize the results obtained. We found four CD45 expression patterns: very low in typical CLL; relatively low in MCL; intermediate intensity in MZL, LPL, and FL; very high expression in HCL. Among the atypical cases, very high CD45 expression was found in one case of CD23-negative CLL, in CD23-positive MCL, and CLL with atypical morphology. The results indicate different levels of maturation in low-grade NHL and may help to characterize such neoplasias.
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PMID:CD45 expression in low-grade B-cell non-Hodgkin's lymphomas. 1769 74


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