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 majority of low-grade non-Hodgkin's lymphomas (NHL) undergo clinical progression toward intermediate- and high-grade lymphomas. This progression is often associated with histologic transformation from follicular to diffuse-type NHL. The pathogenetic mechanisms underlying this evolution are presently unknown. In this study, we have analyzed the role in NHL progression of relevant genetic lesions affecting proto-oncogenes and tumor suppressor genes. Sequential biopsies from 21 patients with clinical progression with (5 cases) or without (16 cases) evidence of histologic transformation were analyzed for karyotypic changes, c-myc rearrangements and deletions affecting 6q27 by Southern blot analysis, and p53 mutations by single-strand conformation polymorphism (SSCP) analysis coupled with direct sequencing of polymerase chain reaction-amplified products. No novel cytogenetic aberration was detected in association with progression, and all samples analyzed displayed a normal c-myc gene. Mutations of the p53 gene were detected in 4 of 5 cases displaying histologic transformation from follicular to diffuse-type NHL and in none of the 16 cases displaying clinical progression in the absence of histologic transformation. In 1 of these positive cases, the same mutation was also present in the pretransformation biopsy, correlating with the presence of diffuse-type areas within a predominant follicular pattern. In 1 of these cases, a deletion of 6q27 was also detected in the posttransformation biopsy along with a p53 mutation. These findings indicate that p53 mutations are associated with and may be responsible for histologic transformation of follicular lymphoma.
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PMID:p53 mutations are associated with histologic transformation of follicular lymphoma. 840 Feb 81

Ocular adnexal lymphoproliferative lesions consist of a spectrum of disease entities, including reactive lymphoid hyperplasia, atypical lymphoid hyperplasia, and lymphoma. No clinical or radiologic criteria facilitate a distinction among these lymphoproliferative lesions. The two hyperplastic processes may evolve to localized or systemic lymphoma. A similar pattern is evident in other mucosa-associated lymphoid tumors elsewhere in the body. Most ocular adnexal lymphomas are small lymphocytic non-Hodgkin's tumors with an indolent course; frequently, they remain localized to the ocular adnexa. In comparison, intermediate- and high-grade lymphomas are less common in the ocular adnexa but more aggressive. An approach to the diagnosis and treatment of these complex entities is suggested. Despite new pathologic classification schemes, immunophenotypic labeling, and molecular genetic analysis, the prognosis for patients with small-cell lymphoma in the ocular adnexa is difficult to predict.
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PMID:Ocular adnexal lymphoproliferative lesions. 841 50

The bcl-2 gene is rearranged in most cases of follicular lymphoma and the breakpoint clusters into two specific regions: mbr and mcr. Rearrangements to immunoglobulin heavy chain genes (IgH) result in a deregulation of the gene and increased transcription of mRNA for the bcl-2 protein. In chronic lymphocytic leukaemia (CLL) expression of bcl-2 protein is increased but rearrangement of the gene can be found only in a minority of cases: commonly a variant translocation with a breakpoint region located 5' of the bcl-2 gene (vcr) with preferential rearrangement to immunoglobulin light chain genes. We have analysed breakpoints in mbr and vcr in malignant cells from 96 patients with B-CLL, 45 with hairy cell leukaemia (HCL) and 41 with high- and low-grade non-Hodgkin's lymphomas (NHL). Vcr rearrangements were observed in nine patients (12%) with B-CLL. Four patients had co-migration of rearranged bcl-2 bands to kappa genes and two patients to IgH. Cytogenetic abnormalities involving 18q21, the site of the bcl-2 gene, was found in two cases only. In several cases with bcl-2 gene rearrangement chromosomal aberrations not including 18q21 were observed. In six patients (two B-CLL, one follicular lymphoma, one immunocytoma and two high-grade lymphomas), breakpoints in both vcr and mbr were found. In HCL a rearrangement in the vcr region was found in one case. Bcl-2 protein immunostaining of B-CLL showed intense bcl-2 expression in all cases and no correlation was found between gene rearrangement and protein expression. Our study confirms that breakpoints in the bcl-2 gene commonly cluster to the vcr region in B-CLL, but in most cases over-expression of bcl-2 protein has to be explained by other mechanisms than bcl-2 gene rearrangement. We also report that simultaneous breakpoints in mbr and vcr is a recurrent phenomenon in B-CLL and in other high- and low-grade non-Hodgkin's lymphomas.
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PMID:Bcl-2 rearrangements with breakpoints in both vcr and mbr in non-Hodgkin's lymphomas and chronic lymphocytic leukaemia. 861 30

Non-Hodgkin's lymphomas (NHL) are a heterogeneous group of disorders which can either be classified according to their biology, represented by corresponding counterparts of normal lymphocyte development as in the Kiel classification, or according to their clinical course, used in the Working Formulation. The recently proposed Revised European-American Lymphoma (R.E.A.L.) classification may unify both aspects and facilitate the comparability of international studies. Besides histology, the extent of disease still comprises the major determinant of therapy. In high-grade lymphomas combination chemotherapy with cyclophosphamide, hydroxydaunorubin, vincristine and prednisone (CHOP) represents the treatment of first choice, and may be restricted to 3-4 cycles in patients with limited stages of the disease when followed by involved field radiotherapy. In more extended, bulky stage II to IV disease, treatment must be extended to six courses of CHOP and, potentially, additional irradiation. Even in advanced states of the disease, long-term remission and potential cure are achieved in 30-50% of cases. In low-grade lymphomas, most patients present with advanced stages III and IV for which chemotherapy can be applied with palliative intention only. Hence, a watch-and-wait approach still seems appropriate outside clinical investigations until the disease requires a therapeutic intervention. This consists preferentially of chemotherapy of moderate intensity such as cyclophosphamide, vincristine and prednisone (COP) or prednimustine and mitoxantrone (PmM). In responding patients, maintenance therapy with interferon-alpha is currently being explored and may result in prolongation of disease-free and, possibly also, overall survival. In both high- and low-grade lymphomas, intensification of therapy by myeloablative chemotherapy or combined chemoradiotherapy followed by autologous bone marrow transplantation (ABMT) or peripheral stem cell transplantation provides a promising and potentially curative prospective. In addition, new cytostatic agents such as the purine analogues--fludarabine, chlorodeoxyadenosine and deoxycoformycin--enlarge the therapeutic spectrum. More experimental approaches consist of the application of immunotoxins or radioisotypes, coupled to monoclonal antibodies directed against lymphoma-specific antigens. Overall, the substantial advances that have been achieved in the understanding of the biology and pathogenesis of malignant lymphomas, as well as the current achievements of therapy and the new promising perspectives, justify the hope that curative therapy can soon be offered to an increasing proportion of patients with NHL.
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PMID:Non-Hodgkin's lymphomas--current status of therapy and future perspectives. 865 30

Among non-Hodgkin's lymphomas, primary mediastinal large B-cell lymphoma (PMLCL) has been considered a separate entity that has specific clinical and histological aspects and a poor prognosis. In this study, we reexamined the clinicopathologic features and the response to current treatment of 141 PMLCL and compare them with 916 nonmediastinal large B-cell lymphomas (NMLCL) recorded in the same period and treated with similar combined chemotherapy. The clinical features of PMLCL at diagnosis were largely homogeneous and distinct from NMLCL, with a predilection for young women (59% with a mean age of 37 years versus 42% with a mean age of 54 years), bulky tumor (77% versus 7%, p < 10(4)), high serum lactic dehydrogenase (LDH) level 76% versus 51%, p < 10(4)), and frequent intrathoracic extension to adjacent organs such as pleura, pericardium, and lung. By contrast, extrathoracic or hematologic dissemination was uncommon (2% of bone marrow involvement versus 17%). All patients had diffuse large B-cell nonimmunoblastic, nonanaplastic lymphomas. Histological analysis of the 141 PMLCL evaluated two common patterns: the presence of large cells with clear cytoplasm (found in 38% of cases) and the presence of fibrosis (marked in 25% of cases). The presence of clear cells or intense fibrosis did not constitute prognostic indicators. Immunologic and molecular analysis assessed the profile of bcl-2 expression and the presence of Epstein-Barr virus (EBV) in PMLCL: 30% expressed a high level of bcl-2 protein; EBER RNAs were detected by in situ hybridization in only two of the 41 cases tested. Monotypic light chain restriction could be demonstrated in seven of the 41 PMLCL tested on fixed-section. Treated with polychemotherapy regimens without radiotherapy, 79% of PMLCL patients achieved a complete remission compared with 68% in the NMLCL patient group (p = 0.01). Overall, 3-year survival rates were estimated at 66 and 61%, respectively (p = 0.05), and disease-free survival rates were not significantly different (61 versus 64%). Stratified analysis on the International Prognostic Index (based on age, tumor stage, serum LDH level, and performance status) showed no difference in the overall and disease-free survivals between the two lymphoma groups. In conclusion, PMLCL can be combined with other diffuse large B-cell lymphomas on morphologic grounds; it is not associated with EBV. It responds favorably to treatment and should be managed like other high-grade lymphomas of equivalent histology. However, the uncommon clinical presentation makes it a distinct entity.
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PMID:Primary mediastinal large B-cell lymphoma. A clinicopathologic study of 141 cases compared with 916 nonmediastinal large B-cell lymphomas, a GELA ("Groupe d'Etude des Lymphomes de l'Adulte") study. 866 37

Lymphoid neoplasia is a complex area comprising multiple diseases with varied pathology, treatment, and outcome. The non-Hodgkin's lymphomas are reviewed here. Non-Hodgkin's lymphomas, collectively, represent the sixth most common cancer in the United States as well as the sixth most common cause of cancer deaths. The overall incidence of non-Hodgkin's lymphoma has risen steadily over the past four decades. Although some of this is attributable to human immunodeficiency virus (HIV)-associated lymphoma, HIV-associated disease accounts for only a small part of the increase in lymphoma. As our knowledge of normal as well as neoplastic lymphoid development has expanded on the basis of histopathology as well as adjunct cellular and molecular techniques, multiple classifications have been proposed to take these into account. The clinical relevance to our understanding of non-Hodgkin's lymphoma is the concept that various lymphoid cancers are counterparts of stages of normal lymphoid development. Stages of lymphoid development in terms of cell surface markers and immunoglobulin gene rearrangements have been well characterized. These are particularly applicable to the early B-cell development, which is antigen-independent and occurs in the bone marrow. Diseases correlating with these stages are largely acute lymphocytic and lymphoblastic leukemia/lymphoma and high-grade lymphomas, such as Burkitt's lymphomas. Much has been learned recently about subsequent antigen-dependent B-cell development in secondary lymphoid organs to improve our understanding of the corresponding stages of B-cell neoplasia. Many of these stages correlate with more recently described entities such as mantle cell and marginal zone lymphomas. Histologic study remains crucial in determining the subtype of NHLs, whereas immunohistochemistry, surface phenotype, and molecular studies are useful in selected cases. Although some lymphoma classifications may be better in terms of understanding the lymphoma biology, the working formulation remains useful to guide clinical decision making. Lymphomas classified as low grade are considered incurable with standard therapy when diagnosed, as is usual, at advanced stages. Different subtypes may have different median survivals, but the goal has typically been palliation, whereas experimental approaches are clearly needed. Intermediate and high-grade lymphomas are potentially curable with aggressive combination chemotherapy. Recent evidence suggests that CHOP chemotherapy is as effective as more complex regimens. Still, 40% to 50% of patients are cured. Prognostic factor analysis has allowed separation of subgroups with much better survival in whom CHOP is adequate versus those with much poorer survival in whom experimental approaches are rational. Additional subtypes of lymphomas have been described and characterized since the working formulation was developed, including mucosa-associated lymphoid tissue tumors (MALT-oma), mantle zone lymphoma, anaplastic large cell lymphoma and AILD-like T-cell lymphoma. Approaches to these entities are still being optimized. Newer approaches, including high-dose therapy with stem cell support, biologic agents, and newer chemotherapeutic agents are discussed, as are special situations such as localized lymphoma of certain sites and lymphoma in immunosuppressed patients.
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PMID:Non-Hodgkin's lymphoma. 891 70

The present study examined whether growth characteristics of diffusely growing non-Hodgkin's lymphomas (NHL) may differ as a function of stage. Among 105 NHL of various types and sub-types (REAL [Revised European-American Lymphoma] classification), localized (Ann Arbor pathologic stages I + II) lymphomas exhibited clearly higher indices for mitotic activity, apoptosis and cell turnover, as well as a significantly lower percentage of cells containing immunohistochemically detectable bcl-2 protein, than disseminated (stages III + IV) NHL. A similar pattern emerged when high-grade (Kiel classification) lymphomas only were evaluated. Low-grade NHL showed analogous, but less marked, stage-dependent characteristics, with the exception of median percentages of bcl-2+ cells, which remained comparable in all stages. Our findings are consistent with the notion that dissemination of diffusely growing NHL is usually associated with reduced cell turnover and, in high-grade lymphomas, with the generation of longer-lived cells.
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PMID:Stage-related differences of mitotic and apoptotic indices, and bcl-2 protein expression in diffusely growing non-Hodgkin's lymphomas. 894 12

In the Revised European American Lymphoma (REAL) classification, several subtypes of high-grade lymphomas were combined in the entity diffuse large cell lymphoma (DLL). In the present study, a total of 19 cases of DLL (10 cases of centroblastic lymphoma, 5 cases of mediastinal B cell lymphoma, 2 cases of immunoblastic lymphoma, 1 case of T cell-rich B lymphoma and one case of large cell anaplastic lymphoma) were analyzed for somatically mutated immunoglobulin V region genes. Somatic mutations are acquired in the course of the germinal center (GC) reaction and are thus found in GC B cells and their descendants, i.e. memory B cells. The V gene sequences revealed that the tumor cells of all five subtypes of DLL harbored mutated V region genes and are thus derived from antigen-experienced (post) GC B cells. This indicates that from the point of view of the stage of development of the tumor precursor, the combination of those five subtypes to one entity, i.e. DLL, seems reasonable. In some cases, an unusually high frequency of somatic mutations was detected. This may indicate that DLL are derived from GC B cells, which, due to transforming events, stayed in the GC for prolonged periods of time, thereby accumulating a high load of somatic mutation. An analysis of the mutation pattern suggests that the tumor clone or its precursor were selected for antibody expression while acquiring somatic mutations. The latter observation discriminates DLL from classical Hodgkin's disease, where we recently also observed a high load of somatic mutation within rearranged V region genes, but a frequent occurrence of crippling mutations.
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PMID:Diffuse large cell lymphomas are derived from mature B cells carrying V region genes with a high load of somatic mutation and evidence of selection for antibody expression. 920 91

Non-Hodgkin's lymphomas (NHLs) in man are on the increase. They are also common in dogs, which, as close companions of man, may constitute a useful experimental model. However, comparisons cannot be made without a reliable morphological and immunological classification of canine NHL. Canine NHLs (n = 134) were classified on the basis of fine-needle lymph-node aspirates according to the Kiel classification, and 92 were re-classified according to the Working Formulation and the updated Kiel classification, in a histological and immunological study. The immunophenotype was determined (1) in 92 cases by the use of the pan-T anti-CD3 polyclonal antibody and the pan-B anti-mb1 monoclonal antibody on paraffin wax-embedded tissue sections, and (2) in 47 cases by the use of a panel of polyclonal and monoclonal antibodies on fresh preparations and frozen tissue. Cytological analysis showed a predominance of high-grade lymphomas (73.9%) over low-grade lymphomas (26.1%); it also demonstrated forms not reported in other species (small-cell variants, lymphomas with macronucleolated medium-sized cells [MMCs], and polymorphic lymphomas with a centroblastic component). Histological examination revealed the rarity of follicular lymphomas (2.2% of cases), an appearance suggestive of T-cell neoplasia (8.7% of cases), and evidence that some MMC lymphomas originated in the marginal perifollicular zones. Some (26%) of the lymphomas were of the T-cell phenotype: the majority of these consisted of small-cell, low-grade lymphomas and mycosis fungoides, the rest being either high-grade pleomorphic lymphomas (mixed or large-cell) or, rarely, high-grade, small noncleaved-cell, plasmacytoid lymphomas. No lymphoma expressed a double (T and B) phenotype. This study revealed similarities with, but also notable differences from, human NHL. In particular, the MMC lymphomas may constitute an interesting equivalent of human marginal zone B-cell lymphomas.
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PMID:Cytohistological and immunological classification of canine malignant lymphomas: comparison with human non-Hodgkin's lymphomas. 926 43

Primary lymphomas of the gastrointestinal tract represent 9% of all non-Hodgkin lymphomas, and of these only 3% arise in the rectum or anus. In contrast to their rare occurrence in the general population, the incidence of anorectal lymphomas in patients with acquired immune deficiency syndrome (AIDS), particularly homosexual patients, may be as high as 26% as reported in our own series of AIDS-associated lymphomas. To determine the characteristics of this entity, we studied 15 cases of primary anorectal lymphoma in AIDS patients and compared them with four cases of anorectal lymphoma unrelated to AIDS. The cases in our study were also compared with the reports of rectal lymphoma in the medical literature over the past 30 years. In the present series, the AIDS patients were all male with a median age of 34 years, human immunodeficiency virus (HIV)-positive, with homosexuality as the main risk factor. The four non-AIDS patients included a woman and had a median age of 66.5 years. Histologically, the anorectal lymphomas in AIDS patients were all high grade, predominantly immunoblastic, and polymorphous. In the non-AIDS patients, only two of four lymphomas were high grade, including one Burkitt type. All tumors were of B-cell phenotype. In the AIDS-associated anorectal lymphomas, the presence of Epstein-Barr virus (EBV) in a latent form was demonstrated by an abundance of Epstein-Barr-encoded RNA (EBER) in 14 of 15 cases and latent membrane protein (LMP) in four cases. All anorectal lymphomas unrelated to AIDS were negative for EBV. The unusual anorectal location of AIDS-associated lymphomas is explainable by the high incidence of preceding traumatic lesions and chronic infections in the area. As a result, EBV-carrying B cells may be attracted to the field providing the cell population that, under the conditions of immune deficiency, is able to give rise to high-grade lymphomas.
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PMID:EBV-associated anorectal lymphomas in patients with acquired immune deficiency syndrome. 929 75


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