Gene/Protein Disease Symptom Drug Enzyme Compound
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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)

A case of non-Hodgkin's lymphoma of polymorphous centroblastic type presenting in a renal allograft is reported. The kidney graft was explanted 10 months after transplantation because of chronic rejection. No other manifestations of lymphoma were found in the recipient. Since the human leukocyte antigen patterns of the renal allograft and the recipient differed at two loci, the donor origin of the malignancy could be clearly demonstrated by immunohistochemistry.
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PMID:Malignant lymphoma of donor origin after renal transplantation: a case report. 174 35

Three sisters developed non-Hodgkin's lymphoma (NHL). Thirteen maternal relatives had adenocarcinomas of various types, predominantly breast and large bowel. Detailed laboratory assessment of this family revealed a variety of immunologic abnormalities. Two lymphoma patients had elevated anti-early antigens (EA) Epstein-Barr virus (EBV) titers. One of the two also had a markedly elevated anti-viral capsid antigen (VCA) EBV titer. The two lymphoma patients were human leukocyte antigen (HLA)-identical, but two unaffected siblings shared the same HLA haplotypes. One of the lymphoma patients and four unaffected family members were anergic; and three unaffected family members had a decreased percentage of T-cells. These data suggest that a subtle disturbance in cellular immune functions may play a causal role in some familial aggregations of malignant lymphoma.
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PMID:Clinical and laboratory observations in a lymphoma-prone family. 359 4

Intensive cytoreductive therapy may be curative in certain hematopoietic malignancies, but its administration is limited by lethal marrow toxicity. Bone marrow transplantation (BMT) provides a way of rescue from this toxicity. The donor may be a human leukocyte antigen (HLA) "matched" sibling (allogeneic), an identical twin (syngeneic), or the patient (autologous). Long remissions and possible cures of 50% to 60% have been reported in acute leukemia after intensive treatment with chemotherapy, with and without total body irradiation, followed by allogeneic BMT. A similar approach has been used in chronic myelocytic leukemia (CML) and in non-Hodgkin's lymphoma with encouraging results. Results are best in younger patients and those transplanted early in their disease (i.e., in the first remission for acute leukemia and in the chronic phase of the disease in CML). Solutions to major problems associated with allogeneic BMT, such as graft-versus-host disease and viral infections, are being actively pursued. Syngeneic BMT avoids some of the above problems, but relapses appear to be greater. Nevertheless, this approach has produced a significant number of cures. Autologous BMT is the newest approach, and the demonstration that marrow may be purged of residual tumor cells by immunologic or pharmacologic means has engendered enthusiasm for this area of clinical therapeutic investigation.
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PMID:Bone marrow transplantation in leukemia. Current status. 638 15

High-grade B-cell-type non-Hodgkin's lymphomas are observed in 5% to 8% of patients positive for the human immunodeficiency virus. Nearly all cases belong to one of the three major histologic types: centroblastic or large noncleaved cell, immunoblastic and Burkitt's lymphoma, or small noncleaved cell. Some cases that are polymorphic are termed high-grade B-cell, not otherwise specified (NOS). The authors determined the immunophenotype of each histologic category of acquired immunodeficiency syndrome (AIDS)-related non-Hodgkins' lymphoma and sought a relationship with the presence of the Epstein-Barr virus (EBV). B-cell differentiation antigens, activation marker expression (human leukocyte antigen-DR, CD10, CD19, CD20, CD21, CD22, CD23, CD25, CD30, CD38), and epithelial membrane antigen were analyzed. The clonality was determined by the detection of cytoplasmic immunoglobulin, surface immunoglobulin, and the analysis of joining region (JH) immunoglobulin gene configuration by Southern blot. Epstein-Barr virus was detected either by Southern blot analysis using BamHI W probe fragment or by in situ hybridization with EBV-encoded RNA transcripts-1 specific probe. The immunophenotypic and genotypic results were compared with the morphology results and with the presence or absence of EBV. Burkitt's lymphomas were associated with EBV in 50% of cases, were monoclonal, and expressed mostly immunoglobulin (Ig) MK, CD10, CD19, CD20, CD22, and CD38. This immunophenotypic profile closely resembled those of the centroblastic cases (large noncleaved cell), in which EBV was absent. Epstein-Barr virus was associated with 90% of immunoblastic cases, and only CD10, CD20, and CD38 were expressed. CD71 was expressed in all categories of non-Hodgkin's lymphoma, and CD21 and CD23 were rarely expressed. Two cases of immunoblastic lymphoma and one case of high-grade B-NOS were polyclonal regarding JH rearrangement, but EBV tested with 1.9-Kb Xhol fragment was clonal. No significant immunophenotypic changes were noted in relation to the presence of EBV. Such studies comparing morphology, immunophenotype, and genotype could help classify and better understand the pathogenesis of AIDS-related non-Hodgkin's lymphoma.
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PMID:Immunophenotypic and genotypic analysis of acquired immunodeficiency syndrome-related non-Hodgkin's lymphomas. Correlation with histologic features in 36 cases. French Study Group of Pathology for HIV-Associated Tumors. 820 68

We report a patient with T-cell non-Hodgkin's lymphoma (NHL) who relapsed after treatment with relatively intensive third-generation chemotherapy, VACOP-B, and who was safely and effectively treated with allogeneic peripheral blood stem cell transplantation (allo PBSCT) with double conditioning. The first conditioning consisted of carboplatin and etoposide. Twenty-one days later, the second conditioning was performed with cytosine arabinoside, cyclophosphamide, and total body irradiation (AraC/Cy/TBI). Between the periods of the first and second conditioning, autologous (auto) PBSCT (4.4 x 10(5) colony-forming units granulocyte/macrophage (CFU-GM)/kg, 3.8 x 10(6) CD34+ cells/kg) was performed to rescue marrow aplasia after the first conditioning. After the second conditioning, allo PBSCT (2.1 x 10(5) CFU-GM/kg, 8.2 x 10(6) CD34+ cells/kg) was performed from a human leukocyte antigen-identical sibling. Marrow reconstitution after allo PBSCT was rapid. Grade I acute graft-vs.-host disease (GVHD) involving skin and chronic GVHD on the eye was observed. No severe transplantation-related complications occurred. With a follow-up of 22 months after allogeneic PBSCT, the patient is alive without evidence of the disease. This case shows that allo PBSCT with intensive double conditioning may become a new treatment strategy to achieve long-term disease-free survival for young NHL patients of resistant relapse with a great deal of tumor burden and invasion of lymphoma cells in bone marrow.
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PMID:Successful treatment of relapsed T-cell non-Hodgkin's lymphoma with allogeneic peripheral blood stem cell transplantation with double conditioning. 1040 85

Different ethnic groups with a high human leukocyte antigen (HLA)-A11 prevalence have been shown to experience a high rate of Epstein-Barr virus (EBV) infection, EBV-associated malignancies, and Epstein-Barr nuclear antigen (EBNA)-4 mutations. The epitopes 399-408 and 416-424 of EBNA-4 are major antigenic epitopes that elicit an HLA-A11 cytotoxic T lymphocyte (CTL) response to EBV infection. Mutations selectively involving one or more nucleotide residues in these epitopes affect the antigenicity of EBNA-4, because the mutant EBV strains are not recognized by the HLA-A11-restricted CTLs. To investigate these mutations in common EBV-associated malignancies occurring in different populations, we studied the mutation rate of epitopes 399-408 and 416-424 of EBNA-4 in 25 cases of EBV-associated Hodgkin's disease (HD), nine cases of AIDS-related non-Hodgkin's lymphoma, and 37 cases of EBV-associated gastric carcinoma (GC) from the United States, Brazil, and Japan. We found one or more mutations in these two epitopes in 50% (6/12) of United States HD, 15% (2/13) of Brazilian HD, 50% (6/12) United States GC and 28% (7/25) Japanese GC, and 22% (2/9) of United States AIDS-lymphoma. Similar mutations were found in 30% (3/10) of United States reactive, 0% (0/6) of Brazilian reactive, and 25% (2/8) Japanese reactive tissues. The most frequent amino acid substitutions were virtually identical to those seen in previously reported isolates from EBV-associated nasopharyngeal carcinomas and Burkitt's lymphomas occurring in high prevalence HLA-A11 regions. However, only 2/28 (7%) mutations occurred in HLA-A11-positive patients. Our studies suggest that: 1) EBNA-4 mutations are a common phenomenon in EBV-associated HD, GC, and AIDS-lymphoma; 2) the mutation rate does not vary in these geographic areas and ethnic groups; 3) EBNA-4 mutations in EBV-associated United States and Brazilian HD, United States and Japanese GC, and United States AIDS lymphomas are not related to patients' HLA-A11 status.
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PMID:Epstein-Barr virus (EBV) nuclear antigen (EBNA)-4 mutation in EBV-associated malignancies in three different populations. 1048 51

The field of radioimmunotherapy for the treatment of non-Hodgkin's lymphoma (NHL) has advanced significantly over the past decade, and several radioimmunoconjugates are being tested in clinical trials. Two of these antibodies target CD20: yttrium-90 (Y-90)-labeled ibritumomab tiuxetan (Zevalin) and tositumomab/iodine-131 (I-131)-labeled tositumomab (Bexxar). Other agents target either CD22 (Y-90 epratuzumab) or human leukocyte antigen (HLA)-DR (I-131 Lym-1), respectively. In February 2002, Y-90-labeled ibritumomab tiuxetan became the first radioimmunoconjugate to be approved by the US Food and Drug Administration (FDA) for the treatment of cancer. Tositumomab/I-131 tositumomab was approved in June 2003. Thus, two radioimmunoconjugates have been approved for the treatment of NHL. Both agents, when administered as a single dose, have produced impressive tumor response rates with an acceptable toxicity profile. The main side effect is reversible myelosuppression. Radioimmunotherapy produces overall response rates of approximately 80% in patients with low-grade lymphomas, and 25% to 30% of patients achieve a complete remission. Lower response rates (approximately 40%) have been reported in patients with large-cell lymphomas. This review discusses the clinical trials of radioimmunotherapeutic agents for NHL that demonstrated their safety and efficacy and outlines the current status of these agents.
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PMID:Radioimmunotherapy: a new treatment modality for B-cell non-Hodgkin's lymphoma. 1520 90

Comparison of human leukocyte antigen (HLA) frequencies in patients with hepatitis C virus (HCV)-associated hepatocellular carcinoma (HCC) and in patients with HCV-associated non-Hodgkin's lymphoma (NHL) has not been addressed previously. To this aim, we investigated the distribution of HLA class II alleles in two selected groups of HCV-infected patients. Group 1 included 50 patients with HCV-associated NHL; group 2 included 29 patients with HCV-associated HCC. A control group included 144 hospitalized patients without NHL or HCC and who were negative for HCV, hepatitis B virus, and human immunodeficiency virus antibodies. Polymerase chain reaction sequence DRB1 and DQB1 specific-primer methods were used. DRB1*1101/DQB1*0301 haplotype, which mainly favors the spontaneous clearance of HCV infection, was lower in HCC subjects than in controls, whereas HLA-DRB1*1104/DQB1*0301, was higher in NHL patients. These findings suggest different pathogenic pathways in HCC and in NHL development. In patients with HCV-associated HCC, a major protective role of DQB1*0301 allele, rather than DRB1*11, was found, probably because of a better HLA class II-associated virus clearance. By contrast, the same allele as HLA-DRB1*04 showed an increase in HCV-associated NHL. These data suggest that NHL and HCC development may be associated to a different response with respect to chronic HLA class II-restricted antigen presentation (perhaps a switch toward CD4+Th2 response in NHL?) or, alternatively, that these alleles could be in linkage disequilibrium to unrelated gene(s), or are in synergy with other immunomodulatory genes that may confer increased risk for NHL.
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PMID:Hepatitis C virus-related hepatocellular carcinoma and B-cell lymphoma patients show a different profile of major histocompatibility complex class II alleles. 1555 90

Plasma levels of beta-2 microglobulin (beta2M), a subunit of the human leukocyte antigen-class I (HLA-I) molecule, correlate negatively with outcome in non-Hodgkin's lymphoma (NHL) and Hodgkin's disease (HD). We examined the clinical relevance of soluble HLA-I (sHLA-I) levels in NHL and HD. Sera from consecutive NHL (n=65) and HD (n=37) patients were analyzed in a blinded manner. NHL and HD patients had significantly higher levels of sHLA-1 and beta2M than control subjects. In NHL patients, sHLA-I levels correlated with clinical behavior in a fashion similar to that of beta2M. However, multivariate analysis incorporating beta2M, sHLA-I, and international prognostic index (IPI) indicated that NHL patients with elevated (>312.6mug/100mL) sHLA-I levels had significantly shorter survival, independent of IPI score as well as beta2M. In HD patients, beta2M but not sHLA-I levels were associated with clinical behavior. These findings not only establish the role of sHLA-I as an independent tumor marker in NHL that can be used to stratify patients, but also suggest that beta2M and sHLA-I may reflect different biological processes in HD and NHL. Further studies are needed to assess whether the immunomodulatory properties of sHLA-I may be responsible for its divergence from beta2M as an indicator of clinical behavior in HD.
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PMID:Clinical relevance of soluble HLA-I and beta2-microglobulin levels in non-Hodgkin's lymphoma and Hodgkin's disease. 1686 Aug 65

A first-generation series of novel small molecules, collectively known as selective high-affinity ligands (SHALs), were designed and synthesized to mimic the binding of Lym-1, a monoclonal antibody (mAb) shown to be an effective cytotoxic and radionuclide carrier molecule for targeting non-Hodgkin's lymphoma (NHL). Created as radionuclide targeting molecules, these SHALs were intended to have the human leukocyte antigen-DR (HLA-DR) selectivity of Lym-1 mAb and the pharmacokinetics of a small molecule. Because of the remarkable bioactivity of Lym-1 in vitro, the direct antilymphoma activity of three of these SHALs was tested. Two of these SHALs were bidentate and consisted of two ligands connected to the carboxyl and amino groups of lysine and polyethylene glycol (PEG); the third SHAL was a dimeric version of one of the former two SHALs linked with PEG. The three SHALs tested were: LeLPLDB, that contained one deoxycholate and one 5-leu-enkephalin as ligands; (LeacPLD)2LPB, a bis version of LeLPLDB intended to improve "functional affinity"; and ItPLDB, that contained the ligands, deoxycholate and triiodothyronine. Micromolar concentrations of all three SHALs showed binding to Raji, an HLA-DR10-positive human malignant B-cell line but no binding to CEM or Jurkat's, HLA-DR10-negative malignant T-cell lines. Additionally, the Raji cell membrane distributions of all three SHALs and of Lym-1 were remarkably similar. Unlike Lym-1, which causes substantial growth inhibition and cell death in NHL cell lines, these SHALs had no direct antilymphoma activity. In summary, three first-generation SHALs lacked direct antilymphoma activity, although they had selective NHL B-cell binding like Lym-1 mAb. Because of their small size, these SHALs have potential as radionuclide carrier substitutes for Lym-1 mAb to target the HLA-DR10 NHL-related cell-surface protein.
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PMID:Direct antilymphoma activity of novel, first-generation "antibody mimics" that bind HLA-DR10-positive non-Hodgkin's lymphoma cells. 1725 80


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