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 transcription factor PU.1 has been shown to be crucial for the early stages of B cell development but its function at later stages of B cell development is less well known. We observed previously that PU.1 is expressed uniformly throughout the mature pre-plasma cell B cell population, the only exception being a subpopulation of germinal centre (GC) cells which showed exceptionally high expression of PU.1. This suggested that PU.1 may also have a role in GC B cell biology. To test this hypothesis and to screen for possible genes regulated by PU.1, we first evaluated semi-quantitatively the possible co-expression of PU.1 with proteins known to be upregulated or downregulated during GC B cell development. Normal lymphoid tissues and 255 B cell non-Hodgkin lymphomas of putative GC B cell origin were evaluated. PU.1 expression was positively associated with CD10 (p < 0.0001), CD20 (p = 0.043), CD22 (p = 0.005), CD79a (p = 0.024) and Bcl-6 (p < 0.0001) and negatively associated with cytoplasmic immunoglobulin light-chain expression (p = 0.036) in diffuse large B cell lymphoma. Identical or nearly identical associations were found in follicular lymphoma. Since CD20 is known to be partly regulated by PU.1 and putative PU.1-binding sites have been described in the regulatory regions of the CD22, CD79a and CD10 genes, we looked for putative PU.1 binding sites in the BCL6 promotor. Four such putative PU.1 binding sites were identified. Further analysis by gel-shift electromobility essay showed that PU.1 protein binds to three of the four putative binding sites in the BCL6 promotor. PU.1 and Bcl-6 were also found to be upregulated in centroblasts in the normal GC, but jointly downregulated in a subpopulation of centrocytes. Our findings support the contention that PU.1 may also have an important role in GC B cell development.
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PMID:PU.1 protein expression has a positive linear association with protein expression of germinal centre B cell genes including BCL-6, CD10, CD20 and CD22: identification of PU.1 putative binding sites in the BCL-6 promotor. 1684 70

We examined the expression of CD20 in normal canine peripheral blood mononuclear cells, normal canine spleen, and canine non-Hodgkin lymphoma (NHL) to determine the feasibility of using this antigen as a diagnostic aid and as a possible target for therapy. An antibody generated against a C-terminal (intracytoplasmic) epitope of human CD20 recognized proteins of 32-36 kd in normal and malignant canine lymphocytes. This antibody showed restricted membrane binding in a subset of lymphocytes in peripheral blood, in the B-cell regions from a normal canine spleen and lymph node, and in malignant cells from 19 dogs with B-cell NHL, but not from 15 dogs with T-cell NHL. The patterns of CD20 reactivity in these samples overlapped those seen using an antibody that recognizes canine CD79a. This anti-CD20 antibody is therefore suitable as an aid to phenotype canine NHL. In contrast, normal canine B cells were not recognized by any of 28 antibodies directed against the extracellular domains of human CD20 (including the chimeric mouse-human antibody Rituximab) or by any of 12 antibodies directed against the extracellular domains of mouse CD20. Thus, the use of CD20 as a therapeutic target will require the generation of specific antibodies against the extracellular domains of canine CD20.
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PMID:CD20 expression in normal canine B cells and in canine non-Hodgkin lymphoma. 1600 6

Rituximab is a chimeric anti-CD20 monoclonal antibody. It has shown efficacy in patients with B-cell non-Hodgkin lymphoma and also in CD20-positive Hodgkin lymphoma. Recently, CD20-negative tumors have been described after Rituximab therapy. We report a 34-year-old man with a history of nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL), treated with different chemotherapy regimens, including anthracyclines and Rituximab. After 4 years in complete remission, he developed a CD20-negative T-cell-rich B-cell lymphoma (TCRBCL) presenting as multiple lung lesions. This case shows the difficulties in the diagnosis of CD20-negative lymphomas when the number of tumor cells is low and when they are found in a predominant T-cell context. Using anti-CD79a as a B-cell marker is mandatory to overcome the difficulties in identifying these tumors. Moreover, this case illustrates the usefulness of laser capture microdissection to obtain purified cell populations for molecular studies in lymphomas with relative paucity of tumor cells, as well as the need to analyze different IgH gene regions to decrease the rate of false-negative results in PCR clonality studies.
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PMID:CD20-negative T-cell-rich B-cell lymphoma as a progression of a nodular lymphocyte-predominant Hodgkin's lymphoma treated with rituximab: a molecular analysis using laser capture microdissection. 1616 Apr 85

Tumor-associated carbohydrates have potential not only as diagnostic tools but also as specific therapeutic targets. Their identification, however, has been hampered by the lack of suitable technologies. We used carbohydrate array technology to compare serum antibody (IgG and IgM) levels against 37 different carbohydrates between classical Hodgkin's lymphoma (cHL) patients and age/sex-matched healthy controls. Serum IgM levels measured by ELISA against 2 of the 5 carbohydrates identified using this technique, L-alpha-arabinose (L-Araf) and alpha-N-acetylgalactosamine (GalNAc(alpha)), were higher (F values of 11.30 and 18.27, respectively) in a cohort of cHL patients (n = 16) than either diffuse large B-cell lymphoma patients (n = 18) or control sera (n = 12). Higher anti-L-Araf IgM levels in cHL patients were associated with cytosine arabinoside treatment (p < 0.05). The GalNAc(alpha) glycotope, Tn, was found to be heterogeneously expressed in the Reed-Sternberg cells of 9/20 (45%) cHL cases, but not in malignant cells of 25 cases of lymphocyte-predominant HL or another 21 hematological disorders (291 cases) examined immunohistochemically. Tn was expressed in 41/238 (17%) classical HL cases present on a tissue microarray. Expression was associated with CD79a and LMP1 expression and negatively with p27(KIP1) expression (p < 0.05). Kaplan-Meier survival analysis revealed a trend towards improved relapse-free survival with Tn expression although this was not statistically significant (p = 0.271). We suggest that this technique could provide a powerful tool for identifying novel carbohydrates in other cancers.
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PMID:Cancer-associated carbohydrate identification in Hodgkin's lymphoma by carbohydrate array profiling. 1639 6

Although Hodgkin lymphoma-like posttransplantation lymphoproliferative disorder (HL-like PTLD) has been grouped with classic Hodgkin lymphoma type PTLD (HL-PTLD), controversy remains as to whether it is truly a form of HL or whether it should be more appropriately classified as a form of B-cell PTLD. Because only few cases of HL-like PTLD have been reported, their pathologic nature and clinical behavior have not been well defined. This report characterized 5 cases of HL-like PTLD with respect to their immunophenotype, EBV status, clonality, and clinical outcome. All of the patients were male, with ages ranging from 1.5 to 55 years at diagnosis. PTLD developed from 4 months to 6 years following solid organ transplantation (3 hearts, 1 kidney, 1 liver), and involved both nodal and extranodal sites. All were EBV-related (EBER+) with the large neoplastic cells CD20/CD79a positive but CD15 negative. Immunoglobulin gene rearrangements were detected in 3 of 5 tested. All patients were managed by initial reduction/withdrawal of immunosuppression, with 2 also receiving chemotherapy for non-HL. Three patients died of progressive disease within 2 to 3 months after diagnosis, 1 is alive and well 2 years later, and the fifth was disease free but died of unrelated causes (graft coronary disease) 2 years later. We conclude that, although HL-like PTLD morphologically simulates classic HL PTLD, there are important immunophenotypic, molecular genetic, and clinical differences, suggesting it is in fact most often a B-cell PTLD. Distinction between HL and HL-like PTLD may be important for clinical management and prognosis.
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PMID:Hodgkin lymphoma-like posttransplant lymphoproliferative disorder (HL-like PTLD) simulates monomorphic B-cell PTLD both clinically and pathologically. 1662 93

DEV is the only cell line derived from nodular lymphocyte predominance type of Hodgkin's lymphoma (NLPHL); however, a comprehensive report about the genetic and immunophenotypic profile of this unique cell line is lacking. We analyzed DEV with respect to immunophenotype and genetic aberrations. The immunostaining revealed positivity for CD45, CD20, CD22, CD79a, IgA2, CD80, CD86, CD74, and BCL6. Cytogenetically, DEV has complex chromosome 3 translocations involving chromosomes 7, 14, and 22. A detailed analysis of the 3q27 breakpoint of the der(3)t(3;14)(p14;q32)t(3;22)(q27;q11.2) revealed a break in the BCL6 alternative breakpoint region. Using array comparative genomic hybridization, a 3-megabase homozygous deletion at 17q24.1-24.2 was identified. Fluorescence in situ hybridization indicated the presence of 2 chromosome 17 homologues, each of which carried a small interstitial deletion. Eight microsatellite markers flanking the homozygously deleted region all showed a homozygous pattern suggesting loss of one of the parental alleles. D17S1809 and D17S1816 could not be amplified using DEV DNA, in keeping with a location within the homozygously deleted segment. In conclusion, DEV has an immunophenotype that is consistent with the neoplastic cells of NLPHL cases, the lymphocytic and histiocytic cells. We demonstrated involvement of the BCL6 gene based on the presence of a breakpoint in the alternative breakpoint region and nuclear staining for BCL6 protein and identified a homozygously deleted region at 17q24.
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PMID:BCL6 alternative breakpoint region break and homozygous deletion of 17q24 in the nodular lymphocyte predominance type of Hodgkin's lymphoma-derived cell line DEV. 1673 7

We describe a composite lymphoma with recurrent Hodgkin lymphoma and diffuse large B-cell lymphoma components manifesting as a single, perforated small intestinal tumor in a 56-year-old man with a history of classical Hodgkin lymphoma and recent relapse in the bone marrow. The resected mass had 2 morphologically and immunophenotypically distinct components; 1 showed a pleomorphic cellular infiltrate with fibrosis and contained numerous, large Hodgkin/Reed-Sternberg-like cells and variants. The tumor cells were CD30+ and focally positive for CD15 but CD20-, CD79a-, and PAX-5-. In situ hybridization for Epstein-Barr virus (EBV) was strongly positive in the large pleomorphic tumor cells. The adjacent component displayed sheets of relatively uniform, large lymphoid cells with typical morphologic features of diffuse large cell lymphoma. The tumor cells showed uniform expression of tested B-cell antigens, absence of CD30 or CD15, and complete absence of EBV-encoded RNA. Separate molecular studies with immunoglobulin heavy and k light chain gene rearrangements clearly demonstrated an identical rearrangement pattern, indicating derivation from the same clone, which was confirmed by direct DNA sequencing analysis. Such distinctly different morphology, immunophenotype, and EBV status in different components within a clonally related single tumor mass is striking.
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PMID:Composite recurrent hodgkin lymphoma and diffuse large B-cell lymphoma: one clone, two faces. 1689 Nov 97

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) differs in histological and clinical presentation from classical Hodgkin lymphoma (cHL). The typical morphologic signs of NLPHL are atypical "lymphocytic and histiocytic" (L&H) cells, which are surrounded by a non-neoplastic nodular background of small lymphocytes of B-cell origin. The NLPHL cells are positive for CD45, CD19, CD20, CD22 and CD79a, but lack expression of CD15 and CD30, the typical markers for cHL. NLPHL patients are predominantly of male gender with a median age of 37 years. Patients often present in early stages (63%) and rarely have B-symptoms (9%). Treatment of NLPHL patients using standard Hodgkin lymphoma (HL) protocols leads to complete remission (CR) in more than 95% of patients. Survival and freedom from treatment failure (FFTF) are worse in advanced-stage patients than in early-stage patients. Thus, patients in advanced and in early stages with unfavorable risk factors are treated similarly to cHL patients. In contrast, patients with early-stage NLPHL without risk factors can be sufficiently treated with reduced intensity programs having less severe adverse effects. As a result, treatment of early NLPHL is less clearly defined, including radiotherapy in extended field (EF) or involved field (IF) technique, combined modality treatment, and, more recently, monoclonal antibody rituximab. Watch and wait strategy plays an important role in pediatric oncology to avoid adverse effects associated with therapy.
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PMID:Biology, clinical course and management of nodular lymphocyte-predominant hodgkin lymphoma. 1712 71

Targeting cytotoxic drugs to cancer cells using antibody-drug conjugates (ADCs), particularly those with stable linkers between the drug and the antibody, could be an effective cancer treatment with low toxicity. However, for stable-linker ADCs to be effective, they must be internalized and degraded, limiting potential targets to surface antigens that are trafficked to lysosomes. CD79a and CD79b comprise the hetrodimeric signaling component of the B-cell receptor, and are attractive targets for the use of ADCs because they are B-cell-specific, expressed in non-Hodgkin lymphomas (NHL), and are trafficked to a lysosomal-like compartment as part of antigen presentation. We show here that the stable-linker ADCs anti-CD79b-MCC-DM1 and anti-CD79b-MC-MMAF are capable of target-dependent killing of nonHodgkin lymphoma cell lines in vitro. Further, these 2 ADCs are equally effective as low doses in xenograft models of follicular, mantle cell, and Burkitt lymphomas, even though several of these cell lines express relatively low levels of CD79b in vivo. In addition, we demonstrate that anti-CD79b ADCs were more effective than anti-CD79a ADCs and that, as hypothesized, anti-CD79b antibodies downregulated surface B-cell receptor and were trafficked to the lysosomal-like major histocompatibility complex class II-positive compartment MIIC. These results suggest that anti-CD79b-MCC-DM1 and anti-CD79b-MC-MMAF are promising therapeutics for the treatment of NHL.
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PMID:Antibody-drug conjugates targeted to CD79 for the treatment of non-Hodgkin lymphoma. 1737 36

Follicular lymphoma (FL) is a neoplasm originating from germinal centre cells, corresponding to 25-40% of non-Hodgkin's lymphomas. Transformation into diffuse large B cell lymphoma (DLBCL) occurs in about one-third of cases. CD5 is expressed in B-chronic lymphoid leukaemia/small lymphocytic lymphoma and mantle cell lymphoma, but can rarely be expressed in conjunction with CD10 in well-documented cases of FL. In this report one case of grade 1 FL is described, which transformed into a DLBCL 6 months after initial diagnosis, with both tumours expressing CD5. In both specimens, neoplastic cells were strongly positive for CD20, CD79a, bcl-2, bcl-6 and CD5 in virtually all cells. CD10 was strongly positive in initial specimens and weakly positive in the DLBCL. Investigation using the PCR confirmed the derivation of the DLBCL from the FL as they presented the same immunoglobulin heavy chain gene rearrangement and the same BCL2-J(H) break point.
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PMID:CD5-positive diffuse large B cell lymphoma arising from a CD5-positive follicular lymphoma. 1751 19


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