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)

New insights into the pathogenesis of lymphoid malignancies have been gained through novel genetic, molecular and immunological techniques. A new classification system for lymphoid malignancies, known as the new World Health Organization (WHO) classification, has been proposed recently based on these findings. The relative incidence of the subtypes of malignant lymphoma is known to differ according to geographic location. Adult T-cell leukemia/lymphoma (ATLL) is a human malignancy associated with human T-cell leukemia virus type 1 (HTLV-1), and the Kyushu islands are an HTLV-1 endemic area. To clarify the relationship between the histological classification and prognosis of lymphoid malignancies, we reclassified previous cases in our department and summarized our previous reports using the WHO classification. Of 933 cases of lymphoid malignancies, 471 (50%) were B-cell lymphoma, 396 (42%) T/natural killer (NK)-cell lymphoma and 41 (4%) Hodgkin lymphoma (HL). Analysis of clinical outcome showed favorable prognosis for HL, intermediate for B-cell lymphoma and poor prognosis for T-cell lymphoma. Among B-cell lymphomas, the commonest type was diffuse large B-cell lymphoma (n = 281; 60%). Marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) was diagnosed in 82 cases (17%), follicular lymphoma in 52 (11%) and mantle cell lymphoma in 24 (5%). Other less common lymphomas were Burkitt lymphoma (n = 9; 2%) and lymphoblastic lymphoma (n = 5; 1%). Using overall survival rates, the various B-cell lymphoma types could be divided into three broad groups for prognostic purposes: (i) low-risk group comprising follicular lymphoma and MALT; (ii) intermediate-risk group comprising diffuse large B-cell lymphoma and Burkitt lymphoma; and (iii) high-risk group comprising mantle cell lymphoma and lymphoblastic lymphoma. Among the T/NK-cell lymphomas, the commonest type was ATLL (n = 191; 48%), followed by peripheral T-cell lymphoma, unspecified (n = 83; 21%), angioimmunoblastic lymphadenopathy with dysproteinemia (AILD) (n = 38; 10%), anaplastic large cell lymphoma (ALCL) (n = 22; 6%). Less common types were lymphoblastic lymphoma (n = 17; 4%), nasal and nasal-type NK/T-cell lymphoma (n = 17; 4%), mycosis fungoides (MF) (n = 9; 2%) and other rare types. With respect to clinical prognosis, T/NK-cell lymphomas fell into three groups: (i) relative low-risk group comprising ALCL, AILD, MF and lymphoblastic lymphoma; (ii) relative intermediate-risk group comprising NK/T-cell lymphoma and unspecified lymphoma; and (iii) extremely high-risk group comprising ATLL. Among the lymphoblastic lymphomas, B-cell type and T-cell type lymphomas exhibited different clinical outcomes. We conclude that the histological, phenotypic and genotypic classification of the new WHO system should be beneficial for the clinical approach to these tumors.
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PMID:The World Health Organization classification of malignant lymphoma: incidence and clinical prognosis in HTLV-1-endemic area of Fukuoka. 1194 Feb

Mantle cell lymphoma is one of the most difficult to treat of all the non-Hodgkin's lymphomas. CAMPATH-1H, a humanized monoclonal antibody against the CD52 antigen, has been used with some success in other lymphoproliferative diseases, especially chronic lymphocytic leukemia. This report demonstrates that tumor samples from patients with mantle cell lymphoma express the CD52 antigen and suggests that CAMPATH-1H should be studied in patients with mantle cell lymphoma.
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PMID:CD52 expression in mantle cell lymphoma. 1199 66

We report two cases with B cell malignancies (case #1: refractory mantle cell lymphoma; case #2: lymphocyte predominant Hodgkin's disease (LPHD)) who developed neutropenia post-Rituximab therapy in a setting of significant infiltration of the peripheral blood (PB) and bone marrow (BM) by T cells with an immunophenotype of large granular lymphocytes. Possible pathogenetic mechanisms are discussed.
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PMID:Evidence for T-large granular lymphocyte-mediated neutropenia in Rituximab-treated lymphoma patients: report of two cases. 1200 8

Few cytogenetic data are available concerning the chromosomal constitution of post-transplant lymphomas. We report two paediatric cases of trisomy 3, as a primary anomaly, in post-transplant lymphoproliferative disease (PTLD) associated with B immunophenotype. Using cytogenetic analysis and fluorescence in situ hybridization on chromosome preparations, we found trisomy 3 in both patients and an extra X chromosome in one. Clinical, histological and immunophenotypical data are presented. Trisomy 3 has been observed in different types of non-Hodgkin's lymphomas but it is relatively rare in B-cell lymphomas, with the exception of marginal zone lymphoma and mantle cell lymphoma. To our knowledge, trisomy 3 is an uncommon cytogenetic finding in PTLD. Further cytogenetic studies of these lymphoproliferative disorders might contribute to evaluate the role of these chromosomal anomalies in the pathogenesis of this disease.
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PMID:Trisomy 3 in two paediatric post-transplant lymphomas. 1202 22

A 73-year-old man noticed a subcutaneous tumor on the left upper palpebra from April 1998, but did not seek therapy for it. Facial subcutaneous tumors appeared from November 1999, and multiple tumors appeared on the skin of the chest and both upper arms from January 2000. Tumor biopsy revealed that these tumors were non-Hodgkin lymphoma showing CD19 (+), CD20 (+), CD5 (+), CD10 (-), smIgM (+), sm lambda (+) and cyclin D1 (+). The karyotype was t(11;14) (q13;q32), but bcl-1 gene rearrangement was not detected. On the basis of these data, primary mantle cell lymphoma (MCL) of the subcutis was diagnosed. The patient underwent eight courses of THP-COP therapy, and complete remission was achieved. Primary subcutaneous B-cell lymphoma, especially MCL, is rare. MCL is aggressive and difficult to cure; the median survival of patients is 3 to 5 years, and the 5-year survival is 30%. However, the present patient showed a good response to chemotherapy, and complete remission has continued for 17 months since the MCL was first diagnosed.
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PMID:[Primary subcutaneous mantle cell lymphoma treated successfully with THP-COP therapy]. 1209 92

Mantle cell lymphoma (MCL) is a distinct type of B cell malignancy and accounts for approximately 5-10% of non-Hodgkin's lymphomas (NHL). The characteristic cytogenetic aberration in MCL is the translocation (11;14)(q13;q32) present in virtually all cases. This rearrangement at the BCL1 locus at 11q13 dysregulates the gene CCND1 following juxtaposition with immunoglobulin heavy chain (IGH) transcriptional enhancers at 14q32 and leading to overexpression of its protein product, cyclin D1, which plays a key role in the control of the cell cycle. Eight continuous cell lines (plus several sister cell lines) have been hitherto established from lymph nodes or peripheral blood of patients with MCL (n=5) or with a lymphoma which would nowadays be classified as MCL (n=3). Six of these cell lines carry the specific t(11;14) translocation and a seventh cell line while being negative for t(11;14) shows a rearranged BCL1 locus and cyclin D1 overexpression. Each of these MCL cell lines is unique with regard to its immunophenotypical, additional cytogenetic and functional features. In light of the relatively low frequency of this lymphoma and the poor results of current treatment strategies, the availability of various types of MCL-derived cell lines for immunologic, cytogenetic, molecular and functional studies is expected to illuminate the biology of this disease, which in turn will be hopefully translated into new and better therapies.
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PMID:Malignant hematopoietic cell lines: in vitro models for the study of mantle cell lymphoma. 1212 50

The proteasome, which plays a pivotal role in the control of many cell cycle-regulatory processes, has become the focus of new approaches to the treatment of cancer, including B-cell malignancies, and the first proteasome inhibitor, bortezomib (VELCADE; formerly PS-341), has entered clinical trials. The proteasome controls the stability of numerous proteins that regulate progression through the cell cycle and apoptosis, such as cyclins, cyclin-dependent kinases, tumor suppressors, and the nuclear factor-kB. By altering the stability or activity of these proteins, proteasome inhibitors sensitize malignant cells to apoptosis. Bortezomib is a dipeptidyl boronic acid proteasome inhibitor that effectively and specifically inhibits proteasome activity. In preclinical studies, bortezomib and other proteasome inhibitors have shown activity against a variety of B-cell malignancies, including multiple myeloma, diffuse large B-cell lymphoma, mantle cell lymphoma, and Hodgkin's lymphoma. These agents can induce apoptosis and sensitize tumor cells to radiation or chemotherapy. Based on these findings, phase I clinical trials were conducted with bortezomib in various solid and hematologic malignancies. In these studies, bortezomib was generally well tolerated with manageable toxicities. Phase II trials have been initiated for relapsed and refractory multiple myeloma, refractory chronic lymphocytic leukemia, and non-Hodgkin's lymphoma. Preliminary data from the multiple myeloma phase II study indicate that a significant number of patients responded to therapy or exhibited stable disease and that the drug had manageable toxicities. These findings, along with extensive preclinical data, suggest that bortezomib and other proteasome inhibitors may have far-reaching potential in the treatment of various cancers, including B-cell malignancies.
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PMID:Proteasome inhibitors in the treatment of B-cell malignancies. 1214 56

Recent classifications of non-Hodgkin's lymphomas (NHL) have strictly individualized mantle cell lymphoma (MCL) on the basis of a combination of morphologic, immunophenotypic, and cytogenetic criteria. This clinicopathological entity now appears to be a biological and therapeutic model for the understanding and treatment of hematologic malignancies. The lymphomogenesis of MCL could be explained by a series of genetic abnormalities which occur at different steps of the disease: (1) mutation and/or loss of the ATM gene in centrocytic cells of the follicle mantle of lymph nodes, leading to the loss of ATM function, particularly involved during the V(D)J recombination process; (2) a t(11;14)(q13;q32) translocation which induces a constitutive Bcl-1/PRAD1/CCND1 expression, responsible for cell cycle activation of centrocytic cells characteristic of typical MCL; and (3) secondary additional chromosomal aberrations, such as a p53 mutation, observed in blastic transformation of MCL. Despite the evaluation of a number of treatment modalities, the optimal management of MCL has not yet been defined: (1) conventional and intensified chemotherapy and monoclonal anti-CD20 antibody therapy appear to be effective for the improvement of response rates and event-free or overall survivals; (2) combinations of different treatment modalities must be tested to modify the natural dismal outcome of the disease; and (3) innovative approaches should be developed. From this point of view, all these considerations offer a fine opportunity for extensive medical reflection.
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PMID:Mantle cell lymphoma: a biological and therapeutic paradigm. 1215 64

To assess the sensitivity of primary non-Hodgkin lymphoma cells to rituximab-mediated cytotoxicity, we compared the potency of several rituximab-mediated killing mechanisms on fresh lymphoma cells. All lymphoma cells tested were equally sensitive to antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-mediated phagocytosis of tumor cells, and rituximab-induced apoptosis. However, they were differentially lysed by complement-dependent cytotoxicity (CDC). We found that taking into account both CD20 and complement regulatory protein expression on tumor cells could predict CDC sensitivity in vitro. Importantly, the sensitivity of lymphoma cells to CDC was consistent with the reported different clinical response rates of lymphomas: rituximab induced high CDC killing of follicular lymphoma cells, whereas mantle cell lymphoma and diffuse large cell lymphoma cells were moderately sensible to CDC, and small lymphocytic lymphoma cells were almost all resistant. We propose that CDC is a determinant mechanism of rituximab-induced killing in vivo. Poor sensitivity to CDC in vitro might predict a poor clinical response, whereas high sensitivity to CDC would only indicate a likelihood of response to rituximab treatment.
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PMID:In vitro mechanisms of action of rituximab on primary non-Hodgkin lymphomas. 1239 72

We report the outcome of reduced-intensity allogeneic progenitor cell transplantation (alloPCT) for 188 patients with lymphoma from the Working Party Lymphoma of the European Group for Blood and Bone Marrow Transplantation (EBMT). The median age of the patients was 40 years, the median number of prior treatment courses was 3, and 48% of patients had undergone a prior autologous transplantation. Eighty-four percent of the patients received conditioning with fludarabine-based regimens and 10% with the BEAM (BCNU, etoposide, cytosine arabinoside, melphalan) protocol. Full donor chimerism was confirmed in 71% of 100 patients assessed. Acute graft-versus-host disease (GVHD) developed in 37% of patients and chronic GVHD in 17%. A disease response to donor leukocyte infusion (DLI) was seen in 10 of 14 patients. With a median follow-up of 283 days, the overall survival rates at 1 and 2 years were 62% and 50%, respectively. The 100-day and 1-year transplantation-related mortality (TRM) rates were 12.8% and 25.5%, respectively, and were significantly worse for older patients. The probability of disease progression at 1 year for patients with chemoresistant and chemosensitive disease were 75% and 25%, respectively (P =.001). The progression-free survival at 1 year was 46% and was significantly better for those with chemosensitive disease, Hodgkin disease (HD), and low-grade non-Hodgkin lymphoma (NHL). Patients with high-grade NHL, mantle cell lymphoma, or chemoresistant disease had a poor outcome. Reduced-intensity progenitor cell transplantation is associated with a reduced TRM and may control advanced HD and low-grade NHL. A longer period of follow-up is required to determine the benefit of DLI and the graft-versus-lymphoma effect.
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PMID:Chemoresistant or aggressive lymphoma predicts for a poor outcome following reduced-intensity allogeneic progenitor cell transplantation: an analysis from the Lymphoma Working Party of the European Group for Blood and Bone Marrow Transplantation. 1239 26


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