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Query: UNIPROT:Q06643 (non-Hodgkin's lymphoma)
 11,307 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Anaplastic large cell lymphoma (ALCL), CD30+, is a subtype of T-non-Hodgkin's lymphoma (NHL). Its most common form is a classical systemic type that involves multiple nodal and extranodal sites. In this study, morphologic, immunohistologic, and genetic studies were performed on ALCL cases in Pakistani patients. The median age of the patients in this study was 45 years (age range: 5-70 years), with a male to female ratio of 3.4:1. Thirty-seven (37) patients were diagnosed to have Ki-1 (CD30+) ALCL, which constituted 2% of all NHLs and 12.6% of all T-NHLs, over a period of 11 years (January 01, 1992-December 31, 2002). The tumors were of either T- or null-cell type with constant (100%) expression of CD30 (Ki-1). The majority of the cases (89.2%) expressed EMA, whereas 40.5% of the cases expressed either CD45 (LCA), CD45RO (UCHL1), or ALK. The mean age of ALCL patients with null-cell phenotype was 33.8 years as compared to those with T-cell phenotype having a mean age of 36.3 years. Out of the 37 cases diagnosed as ALCL, amplifiable DNA was isolated from 28 cases, which were further assessed for T-cell clonality for T-cell receptor (TCR)-beta, gamma, and immunoglobulin heavy chain (IgH) for the FR2 and FR3 regions. The polymerase chain reaction (PCR) technique demonstrated clonal rearrangement of the TCR beta, gamma, and IgH regions in 15 (53.6%), 11 (39.3%), and 2 (7.1%) ALCL cases, respectively, out of 28 cases. Association of Epstein-Barr virus (EBV) was noted in seven out of 28 cases (25%) of ALCL by PCR, whereas ISH for EBV-encoded nuclear RNA-1 (EBER-1) detected the presence of EBV in two (16.7%) out of 12 cases, where one was T-cell ALCL and the other null-cell ALCL. Immunostaining for LMP-1 could not be performed, because tissue material was not available. In conclusion, our study demonstrated that the prevalence of ALCL in Pakistan is comparable to that reported for some of the Asian communities and by the International Lymphoma Study Group and that EBV could be partly responsible for the pathogenesis of ALCL.
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PMID:Prevalence and characterization of anaplastic large cell lymphoma and its association with Epstein-Barr virus in Pakistani patients. 1564 4

Primary bladder non-Hodgkin's lymphoma (NHL) is rare. Optimal management remains controversial. Using the Scotland and Newcastle lymphoma group database, 12 patients with primary bladder lymphoma were identified between 1980 and 2001, the largest single group of patients available to date. Histology and immunocytochemistry was reviewed in 9 of the 12 cases. Six cases were low-grade extranodal marginal zone lymphoma, 4 diffuse large B-cell lymphoma, one an ALK 1 positive anaplastic large cell lymphoma (ALKoma) and one a low-grade lymphoma unspecified. Two patients (low-grade NHL) were treated with oral antibiotics (n=1) or diathermy (n=1) alone with complete resolution of disease. One patient with high-grade NHL gained complete remission without conventional therapy. Nine patients were treated with single or combined modality surgery, chemotherapy and/or radiotherapy. Overall survival was 75%, mean follow up of 4.8 (range 1-10) years. A review of 88 additional cases in the literature support the findings that primary bladder lymphoma is associated with a good prognosis. Patients with low-grade extranodal marginal zone lymphoma may respond well to simple therapies. Patients with diffuse large B-cell lymphoma respond well to first-line chemotherapy regimens. Ureteric obstruction and acute renal failure are serious complications. Repeat cystoscopy is mandatory for follow-up.
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PMID:Primary bladder lymphoma: management and outcome of 12 patients with a review of the literature. 1601 32

Heat-shock protein-90 (HSP90) inhibitors are currently being used in phase I clinical trials for treating patients with a variety of neoplasms including lymphomas. Using immunohistochemical methods, we assessed for HSP90 expression in 412 cases of non-Hodgkin's lymphoma. In B-cell lymphomas, HSP90 was moderately to strongly expressed in all cases of Burkitt's lymphoma (5/5, 100%), and in subsets of follicular lymphoma (17/28, 61%), diffuse large B-cell lymphoma (27/46, 59%), nodal marginal zone B-cell lymphoma (6/16, 38%), plasma cell neoplasms (14/39, 36%), small lymphocytic lymphoma/chronic lymphocytic leukemia (3/9, 33%), mantle cell lymphoma (12/38, 32%) and lymphoplasmacytic lymphoma/Waldenstrom macroglobulinemia (3/10, 30%). HSP90 was weakly expressed in six of 14 (43%) cases of extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue. In T-cell lymphomas, HSP90 was moderately to strongly expressed in subsets of anaplastic large-cell lymphoma (14/24, 58%; 9/12 ALK+ and 5/12 ALK-), precursor-T-cell lymphoblastic leukemia/lymphoma (20/65, 31%), unspecified peripheral T-cell lymphoma (8/43, 23%) and angioimmunoblastic T-cell lymphoma (2/17, 12%). HSP90 was weakly expressed in seven of 58 (12%) cases of mycosis fungoides. We conclude that HSP90 is commonly expressed in a subset of many types of B- and T-cell lymphoma. These data suggest that many lymphoma types are suitable targets for modulation of HSP90 activity, and that HSP90 inhibitors are a potential investigational therapy for lymphoma patients.
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PMID:Expression of heat-shock protein-90 in non-Hodgkin's lymphomas. 1605 52

To verify the spectrum of CD99-expressing lymphoid malignancy, an immunohistochemical study for CD99 was carried out in 182 cases of non-Hodgkin's lymphoma, including 21 lymphoblastic lymphomas, 11 small lymphocytic lymphomas, 9 mantle cell lymphomas, 12 follicular lymphomas, 37 diffuse large B cell lymphomas, 18 Burkitt's lymphomas, 28 NK/T-cell lymphomas, 8 angioimmunoblastic T-cell lymphomas, 23 peripheral T-cell lymphomas, unspecified, and 15 systemic anaplastic large cell lymphomas. CD99 was positive in all T-lymphoblastic lymphomas and in 60% of B-lymphoblastic lymphomas. Majority of T and NK cell lymphomas were negative for CD99, except anaplastic large cell lymphomas (ALCLs). Eight of 15 cases (54%) of ALCLs reacted with anti CD99 antibody. Seven of 10 (70%) ALK positive ALCLs expressed CD99, whereas only 1 of 5 (20%) ALK negative ALCLs were positive. Of the mature B-cell lymphomas, 5.4% (2/37) of diffuse large B cell lymphomas and 11.1% (2/18) of Burkitt's lymphomas expressed CD99. In conclusion, CD99 is infrequently expressed in mature B and T cell lymphomas, except ALK-positive ALCL. High expression of CD99 in ALK-positive ALCL is unexpected finding and its biologic and clinical significances have yet to be clarified.
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PMID:Immunoreactivity of CD99 in non-Hodgkin's lymphoma: unexpected frequent expression in ALK-positive anaplastic large cell lymphoma. 1636 3

Chromosomal translocation t(2;5) and the resulting fusion protein nucleophosmin-anaplastic lymphoma kinase (NPM-ALK) are detected in 50% to 70% of anaplastic large cell lymphoma (ALCL), which is a T/null cell non-Hodgkin's lymphoma showing anaplastic morphology with cell surface expression of CD30. Because aberrant CD30 expression was also observed in the T-cell lymphoma derived from lineage-specific NPM-ALK transgenic mice, we tested the hypothesis that there might be a functional relationship between the two neoplastic-related proteins: NPM-ALK and CD30. In this study, we used the RNA interference method to modulate NPM-ALK protein expression in ALCL-derived, t(2;5)-positive Karpas 299 cells. We observed decreased CD30 expression when NPM-ALK was repressed. Further analysis suggested that JunB functioned as the mediator of NPM-ALK-derived CD30 transcriptional regulation. The NPM-ALK-repressed cells, which had low CD30 expression, were characterized with lower cell proliferation compared with cells in the control group, suggesting that altered CD30 expression may correlate to NPM-ALK-mediated tumor cell growth inhibition. Combination of NPM-ALK repression and CD30 ligand leads to significantly increased tumor cell growth inhibition compared with one method alone, suggesting its potential application for ALCL-specific cancer treatment.
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PMID:The expression of CD30 in anaplastic large cell lymphoma is regulated by nucleophosmin-anaplastic lymphoma kinase-mediated JunB level in a cell type-specific manner. 1698 41

ALK (anaplastic lymphoma kinase) is an RTK (receptor tyrosine kinase) of the IRK (insulin receptor kinase) superfamily, which share an YXXXYY autophosphorylation motif within their A-loops (activation loops). A common activation and regulatory mechanism is believed to exist for members of this superfamily typified by IRK and IGF1RK (insulin-like growth factor receptor kinase-1). Chromosomal translocations involving ALK were first identified in anaplastic large-cell lymphoma, a subtype of non-Hodgkin's lymphoma, where aberrant fusion of the ALK kinase domain with the NPM (nucleophosmin) dimerization domain results in autophosphosphorylation and ligand-independent activation. Activating mutations within the full-length ALK kinase domain, most commonly R1275Q and F1174L, which play a major role in neuroblastoma, were recently identified. To provide a structural framework for understanding these mutations and to guide structure-assisted drug discovery efforts, the X-ray crystal structure of the unphosphorylated ALK catalytic domain was determined in the apo, ADP- and staurosporine-bound forms. The structures reveal a partially inactive protein kinase conformation distinct from, and lacking, many of the negative regulatory features observed in inactive IGF1RK/IRK structures in their unphosphorylated forms. The A-loop adopts an inhibitory pose where a short proximal A-loop helix (alphaAL) packs against the alphaC helix and a novel N-terminal beta-turn motif, whereas the distal portion obstructs part of the predicted peptide-binding region. The structure helps explain the reported unique peptide substrate specificity and the importance of phosphorylation of the first A-loop Tyr1278 for kinase activity and NPM-ALK transforming potential. A single amino acid difference in the ALK substrate peptide binding P-1 site (where the P-site is the phosphoacceptor site) was identified that, in conjunction with A-loop sequence variation including the RAS (Arg-Ala-Ser)-motif, rationalizes the difference in the A-loop tyrosine autophosphorylation preference between ALK and IGF1RK/IRK. Enzymatic analysis of recombinant R1275Q and F1174L ALK mutant catalytic domains confirms the enhanced activity and transforming potential of these mutants. The transforming ability of the full-length ALK mutants in soft agar colony growth assays corroborates these findings. The availability of a three-dimensional structure for ALK will facilitate future structure-function and rational drug design efforts targeting this receptor tyrosine kinase.
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PMID:Crystal structure of the ALK (anaplastic lymphoma kinase) catalytic domain. 2063 93

The development of modern molecular biology techniques and their use in characterizing the genetic abnormalities that are of pathogenic significance in non-Hodgkin's lymphoma (NHL) now provides a means to diagnose and rationally subcategorize these neoplasms in addition to the more traditional use of morphologic and immunophenotypic criteria. The shortcomings of traditional methods of NHL diagnosis and classification have been especially evident within the morphological subset commonly referred to as the large-cell lymphomas, which comprise approx 25% and 40% of NHL in children and adults, respectively (1). The marked cytological, immunological, and clinical heterogeneity of this group of tumors suggests that it is comprised of several biologically different neoplasms, but morphological and immunophenotypic subclassification schema have failed to identify meaningful subsets within the large-cell lymphomas. Recently, however, two recurrent genetic abnormalities in large-cell NHL-activation of the BCL6/LAZ3 zinc finger gene located at 3q27 (altered in approx 30% of large-cell lymphomas [2-4]) and the NPM-ALK fusion gene (5-7) produced by the t(2;5)-have been analyzed to now permit the identification of patient subsets that have reproducibly different therapeutic responses and survival rates in most studies, both of these molecular genetic subtypes appearing to have a superior prognosis compared to those cases lacking these gene abnormalities.
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PMID:NPM-ALK Reverse Transcriptase-Polymerase Chain Reaction for Detecting the t(2;5) of Non-Hodgkin's Lymphoma. 2131 8

The diagnosis and classification of non-Hodgkin's lymphoma (NHL) has traditionally been made based on morphologic and mununophenotypic criteria. Unfortunately, because of the diverse nature of this group of diseases, rehante solely on these criteria has frequently resulted in misdiagnosis. In addition, investigators have been limited m their ability to define biologically and clinically relevant non-Hodgkin's lymphoma subgroups using this diagnostic approach. The development of modern molecular biological techniques and their use to characterize the genetic abnormalities that are of pathogenic significance in NHL now provides an additional means to identify and to rationally subcategorize these neoplasms. The shortcomings of traditional methods of NHL diagnosis and classification have been especially evident within the morphological subset commonly referred to as the large-cell lymphomas, which comprise approx 25 and 40% of NHL m children and adults, respec tively (1). The marked cytological, immunological, and clinical heterogeneity of this group of tumors suggests that it is comprised of several biologically different neoplasms. However, morphological and immunophenotypic subclassification of the large-cell lymphomas has failed to identify a subset of tumors having a reproducibly different therapeutic response or patient survival rate. Until recently, recurrent genetic abnormalities characteristic of the large-cell lymphomas had not been identified.However, the characterization during the past 2 yr of chromosomal rearrangements mvolvmg the BCL6/LAZ3 zmc finger gene located at 3q27 (which is altered m approx 30% of these tumors [2,3]), and the cloning by our group (4) of the NPM-ALK fusion gene produced by the t(2;5) may now permrt the identrficatton of molecular genetic subtypes of largecell lymphoma that possess unique btological and/or clinical features.
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PMID:NPM-ALK Reverse Transcriptase-Polymerase Chain Reaction Analysis for Detection of the t(2;5) Translocation of Non-Hodgkin's Lymphoma. 2138 Jun 99

ALK-positive anaplastic large cell lymphoma (ALK+ ALCL) is an uncommon non-Hodgkin's lymphoma of T-cell origin, the majority of which express CD4 and show frequent pan-T-cell antigen loss. While most cases of ALK+ ALCL have the common pattern characterized by anaplastic morphology with hallmark cells, a less common but well-recognized variant with a small cell pattern may pose a diagnostic challenge. We report a case of ALK+ ALCL with small cell morphology and CD8 subset restriction in a 53-year-old male patient who presented primarily with multiple recurrent subcutaneous nodules with histopathologic features simulating a subcutaneous panniculitis-like T-cell lymphoma (SPTCL). The case was initially diagnosed as SPTCL but was reconsidered as ALK+ ALCL when the incidental finding of CD30 positivity on a subsequent biopsy prompted an ALK immunostain, which turned out to be positive in the neoplastic T-cells. The diagnosis of ALK+ ALCL, small cell variant, was then confirmed by detection of an ALK gene rearrangement by FISH analysis. This report highlights a case of ALK+ ALCL with a deceiving clinical and histopathologic presentation, and emphasizes the value of immunohistochemical panel studies and genetic tests in such cases to avoid diagnostic errors.
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PMID:A small cell variant of ALK-positive, CD8-positive anaplastic large cell lymphoma with primary subcutaneous presentation mimicking subcutaneous panniculitis-like T-cell lymphoma. 2176 80

Anaplastic large cell lymphoma (ALCL) accounts for 10% to 30% of all childhood lymphomas and approximately 5% of all non-Hodgkin's lymphoma. ALCL is considered to be a T-cell non-Hodgkin's lymphoma that can be divided into two major groups with distinct genetic, immunophenotypic, and clinical behaviors. The first group consists of a spectrum of CD30+ T-cell lymphoproliferative disorders that include primary cutaneous ALCL (C-ALCL) and lymphomatoid papulosis. The second group is systemic ALCL (S-ALCL), which is further divided into two subgroups: anaplastic lymphoma kinase positive (ALK+) and ALK-negative. Between 30% and 60% of S-ALCL express ALK, which is usually the result of a t(2;5) translocation that correlates with onset in the first three decades of life, male predominance, and good prognosis. Although morphologically similar, ALK- ALCL shows varied clinical behaviors and immunophenotypes; is commonly seen in older age groups, with a peak incidence in the sixth decade of life with no preference as to sex; and has an overall poorer prognosis. We present a case of CD30+, ALK- S-ALCL in a 7-year-old girl.
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PMID:Anaplastic large cell lymphoma: an unusual presentation in a 7-year-old girl. 2196 22


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