Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019829 (Hodgkin's disease)
 30,247 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The bcl-3 gene at chromosome 19q13 encodes a member of the IkappaB family involved in regulating the NFkappaB pathway. Originally identified by its involvement in the rare t(14:19)(q32;q13), BCL-3 expression has never been analyzed in a wide variety of lymphomas. We assessed BCL-3 expression in 353 cases of non-Hodgkin lymphoma and Hodgkin lymphoma using formalin-fixed, paraffin-embedded tissue specimens, a monoclonal antibody specific for BCL-3, and immunohistochemical methods. Of 172 B-cell lymphomas, 10 (6%) were positive for BCL-3, including six of 23 (26%) diffuse large B-cell lymphoma, one of 17 (6%) small lymphocytic lymphoma, one of 26 (4%) follicular lymphoma, and two of 49 (4%) mantle cell lymphoma. All other B-cell neoplasms were negative, including marginal zone lymphoma (n=24, 11 extranodal, nine nodal, four splenic), Burkitt lymphoma (n=10), lymphoplasmacytic lymphoma (n=10), lymphoblastic lymphoma (n=8), and plasmacytoma (n=5). Of 111 T/NK-cell lymphomas, 25 (23%) were positive for BCL-3, including 13 of 40 (32%) anaplastic large-cell lymphoma, three of 10 (30%) angioimmunoblastic T-cell lymphoma, two of eight (25%) extranodal NK/T-cell lymphoma of nasal type, three of 12 (25%) mycosis fungoides, one of five (20%) enteropathy-type T-cell lymphoma, and two of 21 (10%) peripheral T-cell lymphoma unspecified. All other T-cell neoplasms were negative, including lymphoblastic lymphoma (n=6), prolymphocytic leukemia (n=6), and subcutaneous panniculitis-like T-cell lymphoma (n=3). Of 70 Hodgkin lymphomas, of all types, 29 (41%) were positive for BCL-3. The relatively high frequency of BCL-3 expression in some non-Hodgkin and Hodgkin lymphoma types raises the possibility that BCL-3 is involved in the pathogenesis of these tumors, and may be a target of new therapies.
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PMID:Immunohistochemical detection of BCL-3 in lymphoid neoplasms: a survey of 353 cases. 1510 10

T-bet, a T-box transcription factor, is expressed in CD4+ T lymphocytes committed to Th1 T-cell development and in a subset of T-cell non-Hodgkin lymphomas. Recent evidence indicates that T-bet also is expressed in B lymphocytes and might participate in immunoglobulin class switching. We examined T-bet expression in 116 cases of B-cell lymphoproliferative disorders by immunostaining and found that T-bet was expressed consistently in precursor B-cell lymphoblastic leukemia/lymphoblastic lymphoma (14/14 cases) in contrast with precursor T-cell lymphoblastic leukemia/lymphoblastic lymphoma, which is consistently T-bet- (13 cases), as previously reported. T-bet is expressed in memory B cell-derived neoplasms (chronic lymphocytic leukemia, marginal zone lymphoma, hairy cell leukemia; 35/42 cases) but not in cases of mantle cell, follicular, and large cell lymphoma (43 cases). Expression of T-bet in precursor B-cell lymphoblastic leukemia/lymphoblastic lymphoma was confirmed by Western blot analysis. The expression of T-bet in a significant subset of B-cell lymphoproliferative disorders but not in the vast majority of reactive B cells suggests it might have a role in the oncogenesis of T-bet+ B-cell neoplasms. In addition, T-bet should serve as a useful new marker for the diagnosis and subtyping of B-cell lymphoproliferative disorders.
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PMID:T-bet, a T-cell-associated transcription factor, is expressed in a subset of B-cell lymphoproliferative disorders. 1532 32

Low-grade non-Hodgkin's lymphomas of the conjunctiva may be cured by radiotherapy, but complications are frequent and relapses may occur. Other treatment modalities including resection, cryotherapy, injection of interferon-alpha or systemic chemotherapy have been used with varying success. We treated two patients with relapsed extranodal marginal zone lymphoma (ENMZL) of mucosa-associated lymphoid tissue (MALT) of the conjunctiva with the anti-CD20 monoclonal antibody rituximab (375 mg/m2 intravenously once weekly for 4 wk) which has previously been shown to be effective in a variety of other B-cell non-Hodgkin's lymphomas. Treatment was well tolerated and resulted in one partial and one complete remission. With a follow-up of 32 or 30 months, respectively, further recurrences have not been observed. Rituximab is a highly effective and well-tolerated treatment of conjunctival MALT lymphoma, which may not only be of value in relapse, but also in cases of contraindication to radiotherapy.
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PMID:Anti-CD20 monoclonal antibody therapy in relapsed MALT lymphoma of the conjunctiva. 1534 12

ZAP-70 is a tyrosine kinase that participates in early B-cell differentiation and is a prognostic factor in chronic lymphocytic leukaemia (CLL), where it is associated with an unmutated configuration of the IgV(H) genes. In this study ZAP-70 expression was studied by immunohistochemistry in a spectrum of B-cell lymphoid neoplasms; this staining method was compared with flow cytometry, and the relationship of ZAP-70 expression to mutational status and prognosis was assessed. 242 tissue samples from 225 patients with B-cell lymphoid neoplasms arising at different maturational stages were included. Flow cytometry was performed in all CLL cases (n = 52). IgV(H) mutational status was determined in 25 CLL and 12 mantle cell lymphoma (MCL) patients. ZAP-70 was positive in 34/52 (65%) CLL, 9/31 (31%) Burkitt's lymphoma, 2/7 (29%) lymphoblastic lymphomas, 3/36 (8%) MCL, 1/23 (4%) marginal zone lymphoma, and 1/45 (2%) diffuse large B-cell lymphomas, but in none of the 19 follicular lymphomas or the 14 Hodgkin lymphomas. An identical ZAP-70 pattern was obtained in six patients with simultaneous biopsies from different sites and in 12 patients with sequential biopsies. Immunohistochemistry and flow cytometry gave identical results in 48 the 52 CLLs. All but one ZAP-70-positive CLL had IgV(H) gene in an unmutated configuration, whereas all but one ZAP-70-negative CLL had somatically hypermutated IgV(H). The 12 MCLs analysed were ZAP-70 negative regardless of IgV(H) mutational status (4 mutated, 8 unmutated). ZAP-70 positive CLL was associated with a shorter overall survival (median time 103 months vs. 293 months, p = 0.01) and a shorter time to disease progression (median time 26 months vs. 60 months, p = 0.01). In conclusion, ZAP-70 is expressed in several types of B-cell neoplasm and is easily detected by immunohistochemistry, providing a useful prognostic marker in patients with CLL from whom no other material is available or when other techniques for its assessment cannot be performed.
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PMID:Immunohistochemical analysis of ZAP-70 expression in B-cell lymphoid neoplasms. 1568 92

We report a case of mantle cell lymphoma histologically indistinguishable from marginal zone lymphoma. An 83-year-old man presented with a 9.0-cm, slowly enlarging axillary mass. Microscopically, the neoplastic process was largely interfollicular, surrounding residual follicular centers, some of which had discernible small lymphocyte mantles. Overall, the morphologic pattern was highly suggestive of marginal zone lymphoma. However, flow cytometric and immunohistochemical results, including cyclin D1 positivity, revealed an immunophenotype that fit with mantle cell lymphoma. The differential diagnosis of mantle cell lymphoma is broad, and it is well known that mantle cell lymphoma can assume a number of histologic appearances, including, infrequently, that of more indolent B-cell non-Hodgkin lymphomas. Although not pathognomonic, cyclin D1 positivity is highly specific for mantle cell lymphoma and is key in distinguishing these clinically dissimilar malignant lymphomas. In recent years, detection of cyclin D1 has expanded the recognizable histologic spectrum of mantle cell lymphoma.
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PMID:Mantle cell lymphoma disguised as marginal zone lymphoma. 1597 19

Non-Hodgkin lymphomas are among the most common primary tumors occurring in the ocular adnexa. Herein, we present a 14-year single-institution experience in 62 patients with primary ocular adnexal lymphomas (OALs). Association with Chlamydia psittaci infection is examined in 57 tumor specimens. Extranodal marginal zone lymphoma (EMZL) was the most frequent histologic subtype (89%). The majority of patients with EMZL (84%) presented with stage E-extranodal (IE), however only 16% had an advanced stage. All stage IE patients were treated with local radiotherapy, whereas patients with disseminated disease received systemic therapy with or without local irradiation. All but 1 patient with EMZL achieved complete remission (CR). During a median follow-up of 52 months (range, 3-153 months), the estimated 5-year overall survival (OS) and freedom from progression (FFP) were 96% and 79%, respectively. During the follow-up, 22% of patients relapsed, mainly in extranodal sites, and 4% transformed to diffuse large B-cell lymphoma. None of the patients exhibited local orbital failure in the radiation field. None of the OAL specimens harbored C psittaci DNA. Our study demonstrates that EMZLs, accounting for the majority of primary OALs, are characterized by an indolent natural history with frequent, continuous extranodal relapses. In South Florida, OALs are not associated with C psittaci infections.
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PMID:Ocular adnexal lymphoma: a clinicopathologic study of a large cohort of patients with no evidence for an association with Chlamydia psittaci. 1616 88

Extranodal marginal zone B-cell lymphomas of mucosa-associated lymphoid tissue (MALT) lymphomas are a well-described type of low-grade B-cell non-Hodgkin lymphoma. They typically arise adjacent to mucosal surfaces in the gastrointestinal tract, lung and conjunctiva, and, less frequently, in the skin, salivary gland and thyroid gland. Unusual locations, such as the genitourinary tract, thymus and meninges, have also been reported. We recently encountered a case of an intracranial MALT lymphoma in a 53-year-old man who presented with persistent headaches and a seizure. The lesion developed as a mass within the lateral ventricle, appeared to be arising from the choroid plexus, and was not associated with meninges. Histologically, there was a vaguely nodular, dense lymphoid infiltrate with occasional benign follicles colonized by marginal zone lymphoma, suggesting derivation from a focus of prior inflammation. Translocations involving the MALT1 gene were not identified but karyotypic evaluation highlighted a complex cytogenetic profile with many chromosomal abnormalities. This rare case provides insight into the pathophysiology of MALT lymphomas.
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PMID:Extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue arising in the lateral ventricle. 1619 87

B cell-activating factor receptor (BAFF-R) is one of three known receptors for BAFF, a critical regulator of B- and T-cell function. In mice, BAFF-R is required for B-cell maturation and survival, and in mice and humans, the overproduction of BAFF is associated with autoimmune disease. We sought to determine the normal pattern of BAFF-R expression at specific stages of B- and T-cell development and whether this pattern of expression corresponds with related B- and T-cell neoplasms. Most circulating human B cells and a small subset of T cells are BAFF-R-positive. In reactive lymphoid tissues, BAFF-R is expressed by B cells colonizing the mantle zones, by a subset of cells within germinal centers, and rare cells in the interfollicular T-cell zone. BAFF-R is also expressed by B cells colonizing the splenic marginal zone. Seventy-seven (78%) of 116 cases of B-cell lymphoproliferative disorders were BAFF-R-positive by immunohistochemical and/or flow cytometric immunophenotypic analysis, including most cases of mantle cell lymphoma, follicular lymphoma, marginal zone lymphoma, chronic lymphocytic leukemia, hairy cell leukemia, and diffuse large B-cell lymphoma. In contrast, cases of precursor B lymphoblastic lymphoma, Burkitt lymphoma, and nodular lymphocyte-predominant Hodgkin lymphoma exhibit weak to negative staining for BAFF-R. All cases of classical Hodgkin lymphoma and T-cell lymphomas were BAFF-R-negative, including all cases of anaplastic large cell lymphoma, adult T-cell leukemia/lymphoma, angioimmunoblastic T-cell lymphoma, and peripheral T-cell lymphoma, unspecified. These findings highlight BAFF-R as a marker of both normal and neoplastic B cells and raise the possibility that BAFF-R expression is necessary for the survival of a subset of neoplastic B lymphocytes analogous to its known role in promoting normal B-cell maturation and survival.
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PMID:BAFF-R, the major B cell-activating factor receptor, is expressed on most mature B cells and B-cell lymphoproliferative disorders. 1622 12

Malignant lymphomas represent approximately 5% of all malignant neoplasms of the head and neck and may involve nodal or extranodal sites. Nodal head and neck lymphomas are similar to other nodal sites and are not further reviewed here. The head and neck region is the second most frequent anatomical site of extranodal lymphomas (after the gastrointestinal tract). Most are non-Hodgkin's lymphomas of B-cell lineage, and overall diffuse large B-cell lymphoma is the most common type. Hodgkin's lymphoma rarely occurs in extranodal sites. Other hematologic neoplasms that commonly involve extranodal sites of the head and neck are also discussed. In this review, we begin by discussing lymphomas involving the head and neck according to anatomical site. Then we discuss specifically the pathological findings of extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue, plasmablastic lymphoma, extramedullary plasmacytoma, and extranodal natural killer/T-cell lymphoma of nasal type.
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PMID:Extranodal lymphomas of the head and neck. 1630 65

Recent advanced developments in our understanding of cancer cell biology have begun to generate a host of new targets that are proving to be valuable substrates for new drug development. One example includes our ever-increasing understanding of the complex biology surrounding the ubiquitin-proteasome pathway. For years there have been a variety of compounds used in the laboratory that have been shown to inhibit the proteasome, though many of these compounds have proven to be relative non-specific inhibitors of intracellular and proteasome proteases. The recent synthesis of 1 novel inhibitor, bortezomib (formerly known as PS341), has proven to be an effective reversible inhibitor of the chymotryptic protease in the 26S proteasome. Proteasome inhibition represents a new approach for the treatment of many forms of cancer, especially select hematologic malignancies. Bortezomib has been approved by the United States Food and Drug Administration for the treatment of relapsed or refractory multiple myeloma. In addition to myeloma, bortezomib has also shown promising activity in the treatment of select types of non-Hodgkin's lymphomas (NHLs). Several single-agent phase II clinical trials in patients with a host of different NHL histologies have demonstrated that bortezomib has reproducible activity in mantle-cell lymphoma (MCL) and follicular lymphoma (FL), with some suggestion of activity in marginal zone lymphoma. The promising activity in these smaller studies has led to a number of larger multicenter studies with bortezomib in combination with rituximab in MCL, FL, and marginal zone lymphoma. The collective early experience from these studies continues to support the activity of bortezomib in these histologies of NHL. Herein, some of the biologic rationale for using proteasome inhibitors in lymphoma as well as some of the clinical data from these promising studies are discussed.
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PMID:Marked clinical activity of the proteasome inhibitor bortezomib in patients with follicular and mantle-cell lymphoma. 1635 24


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