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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)

Increasing incidence of non-Hodgkin's lymphoma have been associated repeatedly with farming occupation and particular attention focused on the role of pesticide exposure to potentially explain part of this trend. A genetic hallmark of non-Hodgkin's lymphoma is the presence of recurrent chromosomal translocations involving the immunoglobulin heavy chain gene. Of these, the t(14;18), which deregulates BCL2 expression and inhibits apoptosis, is the most frequent in follicular lymphoma and has been detected consistently in peripheral blood lymphocytes of healthy individuals. As BCL2-IGH translocation represents an early step of the malignant process, we evaluated the occurrence and molecular characteristics of BCL2-IGH translocation in 56 individuals occupationally exposed to pesticides in open field farming They were selected from a representative cohort of farmers with a well-defined assessment of pesticide exposure taking into account potential confounding factors, smoking, sunlight, and age. Our results suggest that occupational exposure to pesticides would increase BCL2-IGH prevalence together with the frequency of BCL2-IGH-bearing cells especially during the high pesticide use period. Distribution of BCL2 or IGH breakpoint positions seemed to be independent of pesticide exposure and was similar to those found in other healthy populations or lymphoma patients. Finally, these results provide additional evidence that BCL2-IGH translocation measurements could be a measure of acquired genetic instability in relation to genotoxic exposure in a gene directly relevant in term of lymphomagenesis.
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PMID:Characterization of the t(14;18) BCL2-IGH translocation in farmers occupationally exposed to pesticides. 1502 72

The present study aimed to characterize the clinical and molecular-cytogenetic features of non-Hodgkin's lymphoma (NHL) with double translocation of the immunoglobulin heavy chain (IGH) gene. G-banding analysis, fluorescence in situ hybridization (FISH) with the IGH (Cgamma and VH) and oncogene (c-MYC, BCL1, BCL2, and BCL6) probes, and long-distance polymerase chain reaction (LD-PCR) were performed on 6 patients with B-cell lymphoma, one with angioimmunoblastic T-cell lymphoma, and one with acute lymphoblastic leukemia (ALL) with B-cell phenotype. G-banding analysis detected two different 14q32 translocations, t(14,18) and add (14)(q32) in a patient with ALL. Two distinct partners of double IGH translocation identified by FISH were as follows: c-MYC + BCL2 in 3 patients, c-MYC + BCL1 in 2, c-MYC + BCL6 in one, BCL2 + 9q22 in one, and 1q21 + 6q27 in one. Colocalization of BCL1 and c-MYC probes was demonstrated in a patient with mantle cell lymphoma. LD-PCR detected c-MYC/Cmu, c-MYC/Calpha and BCL6/Cmu, and c-MYC/Calpha fusion in each one patient. Seven of 8 patients showed high serum LDH. Central nervous system and leukemic involvement was observed in 5 and 6 patients, respectively. Median survival time of patients with c-MYC/IGH translocation was 9 months. The results defined a clinical subset of B-cell lymphoma/leukemia showing extremely poor prognosis. C-MYC/IGH translocation is possibly an evolutionary alteration following the primary IGH translocation with BCL1, BCL2, or BCL6. Furthermore, FISH identified one novel (9q22) and one cryptic chromosomal breakpoints (6q27) involved in IGH translocation.
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PMID:Molecular-cytogenetic characterization of non-Hodgkin's lymphoma with double and cryptic translocations of the immunoglobulin heavy chain gene. 1537 Feb 7

Approximately 15% of all cases of childhood classical Hodgkin's disease (HD) express CD20, a B-cell marker associated with immunoglobulin heavy chain rearrangements. Immunoglobulin heavy chain rearrangements in Reed-Sternberg cells could be used to assess minimal residual disease (MRD), as was shown with immunoglobulin heavy chain patient-specific primers (PSPs) in non-Hodgkin's lymphoma. The aim of this study was to analyze pediatric HD for future design of immunoglobulin heavy chain PSP for MRD detection. DNA was extracted from paraffin-embedded tissue from unstained slides of 8 pediatric CD20+ nodular sclerosis HD cases and 10 CD20-nodular sclerosis HD cases. Immunoglobulin heavy chain polymerase chain reaction and sequencing were performed on 16 of 18 cases, which had adequate DNA for further analysis. Sequence analysis from 3 cases (19% of HD cases) demonstrated unique V(D)J regions, which could potentially be used to design PSP. Unique PSPs could be used to assess MRD in advanced-stage HD specimens. Future studies should focus on improved detection and analysis of more cases to identify appropriate specimens in assessing clinical implications of MRD detection.
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PMID:Assessing immunoglobulin heavy chain rearrangements in pediatric CD20-positive and CD20-negative classic Hodgkin's disease. 1563 94

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

The purging efficacy of positive selection of autologous CD34+ PBSC with a clinical scale method of magnetic-activated cell sorting system (CliniMACS) was investigated in 48 patients with non-Hodgkin's lymphoma (NHL). The median purity and recovery rate of the CD34+ cells post-selection were 93.3% (range 32.6-99.3) and 72.2% (range 20.5-309.8), respectively. The real-time PCR method to detect the patient-specific monoclonal immunoglobulin heavy chain gene rearrangement (minimal residual tumor; MRT) and CD19 and CD20 positivities were used for the detection of contaminating NHL cells before and after CD34+ selection. After selection, the median (range) depletion rate of MRT was 2.53 (1.52-4.78) log, and that of CD19+ cell and CD20+ cell was 2.46 (0.74-3.64) log and 2.32 (0.40-4.01) log, respectively. In 41 patients, high-dose chemotherapy was performed, followed by the transplantation of the isolated CD34+ cells. Rapid neutrophil recovery as well as platelet recovery was seen with a median time to reach 0.5 x 10(9)/l neutrophils of 10 days (range 8-13) and 20 x 10(9)/l platelets of 14 days (range 10-34), respectively. The present study demonstrated that CliniMACS is a highly effective positive selection method and a high purging efficacy could be obtained without compromising the hematopoietic reconstitution capacity of the graft in NHL patients undergoing high-dose chemotherapy.
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PMID:Isolation and transplantation of highly purified autologous peripheral CD34+ progenitor cells: purging efficacy, hematopoietic reconstitution in non-Hodgkin's lymphoma (NHL): results of Japanese phase II study. 1565 49

The transcription factor Forkhead box protein P1 (FOXP1) is highly expressed in a proportion of diffuse large B-cell lymphoma (DLBCL). In this report, we provide cytogenetic and fluorescence in situ hybridization (FISH) data showing that FOXP1 (3p13) is recurrently targeted by chromosome translocations. The genomic rearrangement of FOXP1 was identified by FISH in three cases with a t(3;14)(p13;q32) involving the immunoglobulin heavy chain (IGH) locus, and in one case with a variant t(2;3) affecting sequences at 2q36. These aberrations were associated with strong expression of FOXP1 protein in tumor cells, as demonstrated by immunohistochemistry (IHC). The cases with t(3p13) were diagnosed as DLBCL ( x 1), gastric MALT lymphoma ( x 1) and B-cell non-Hodgkin's lymphoma, not otherwise specified ( x 2). Further IHC and FISH studies performed on 98 cases of DLBCL and 93 cases of extranodal marginal zone lymphoma showed a high expression of FOXP1 in approximately 13 and 12% of cases, respectively. None of these cases showed, however, FOXP1 rearrangements by FISH. However, over-representation of the FOXP1 locus found in one additional case of DLBCL may represent another potential mechanism underlying an increased expression of this gene.
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PMID:FOXP1, a gene highly expressed in a subset of diffuse large B-cell lymphoma, is recurrently targeted by genomic aberrations. 1594 19

The BCL3 gene was initially discovered through its involvement in a recurring translocation, t(14;19)(q32;q13), which is found in some patients with B-cell chronic lymphocytic leukemia (B-CLL). The translocation leads to the juxtaposition of BCL3 to the immunoglobulin heavy chain gene locus, resulting in high-level expression of the BCL3 transcript. The Bcl-3 protein includes 7 tandem copies of the ankyrin repeat element in the central domain, a structure that is characteristic of the IkappaB family of inhibitors of the nuclear factor kappaB transcription factors. Anaplastic large cell lymphoma (ALCL) is a subtype of aggressive non-Hodgkin's lymphoma that is characterized by expression of CD30 and the NPM/ALK chimeric protein, which is generated by t(2;5)(p23;q35). We compared the gene expression profiles of ALCL with those of another CD30+ neoplasm, Hodgkin's disease (HD), and found that BCL3 is expressed at higher levels in ALCL than in HD. A comparison by real-time polymerase chain reaction assay revealed that t(2;5)+ ALCL expresses a high level of BCL3 messenger RNA relative to the levels expressed in other hematologic tumors, and the level in ALCL is comparable to or even higher than that in t(14;19)+ B-CLL. An immunohistochemical analysis of ALCL tumor tissues showed that the lymphoma cells exhibited strong nuclear staining by a monoclonal antibody against Bcl-3. We suggest that Bcl-3 sequestrates the (p50)2 homodimer to the nucleus and that the kappaB sites are occupied by the (p50)2/Bcl-3 ternary complex. Future studies should identify the relationships among the 3 independent molecules (ie, NPM/ALK, CD30, and Bcl-3) that are activated in t(2;5)+ ALCL.
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PMID:Reappraisal of BCL3 as a molecular marker of anaplastic large cell lymphoma. 1653 41

In this report, we show that the formation of germinal center (GC)-like structures to thymus-independent type 2 antigens in mice depends on intact signals through CD40, but does not depend on T cell-derived CD40-ligand (CD154). In addition, we show that follicular dendritic cells (FDC) are also critical to thymus-independent GC formation, as their depletion by blockade of lymphotoxin-beta receptor signals abrogated GC development unless the responding B cells bound antigen with high affinity. Further evidence that immune complexes drove this CD40-dependent B cell proliferation was provided by the observation that an antibody that detects immune complexes containing complement component 4 on FDC also inhibited thymus-independent GC formation when injected in vivo at the time of immunization. Finally, we show that thymus-independent B cell proliferation was associated with class switching to IgG3, as IgG3(+) antigen-specific switched B cells could be visualized directly in GC, suggesting that immune complexes can provide the signals for class switching within GC in the absence of CD154.
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PMID:The generation of thymus-independent germinal centers depends on CD40 but not on CD154, the T cell-derived CD40-ligand. 1678 45

Immunotherapy using Rituximab, an unconjugated CD20 monoclonal antibody, has proven effective for treating non-Hodgkin's lymphoma and autoimmune disease. CD19 antibody immunotherapy is also effective in mouse models of lymphoma and autoimmunity. In both cases, mouse models have demonstrated that effector cell networks effectively deplete the vast majority of circulating and tissue B lymphocytes through Fcgamma receptor-dependent pathways. In mice, B cell depletion is predominantly, if not exclusively, mediated by monocytes. CD20 mAbs rapidly deplete circulating and tissue B cells in an antibody isotype-restricted manner with a hierarchy of antibody effectiveness: IgG2a/c > IgG1 > IgG2b >> IgG3. Depending on antibody isotype, mouse B cell depletion is regulated by FcgammaRI-, FcgammaRII-, FcgammaRIII-, and FcgammaRIV-dependent pathways. The potency of IgG2a/c mAbs for B cell depletion in vivo results from FcgammaRIV interactions, with likely contributions from high-affinity FcgammaRI. IgG1 mAbs induce B cell depletion through preferential, if not exclusive, interactions with low-affinity FcgammaRIII, while IgG2b mAbs interact preferentially with intermediate-affinity FcgammaRIV. By contrast, inhibitory FcgammaRIIB-deficiency significantly increases CD20 mAb-induced B cell depletion at low mAb doses by enhancing monocyte function. Thus, isotype-specific mAb interactions with distinct FcgammaRs contribute significantly to the effectiveness of CD20 mAbs in vivo. These results provide a molecular basis for earlier observations that human FcgammaRII and FcgammaRIII polymorphisms correlate with the in vivo effectiveness of CD20 antibody therapy. That the innate monocyte network depletes B cells through FcgammaR-dependent pathways during immunotherapy has important clinical implications for CD19, CD20, and other antibody-based therapies for the treatment of diverse B cell malignancies and autoimmune disease.
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PMID:Fcgamma receptor-dependent effector mechanisms regulate CD19 and CD20 antibody immunotherapies for B lymphocyte malignancies and autoimmunity. 1709 Dec 46

Forty cases of oral cavity non-Hodgkin's lymphoma (NHL) were evaluated for sex, age, location, clinical presentation, and World Health Organization (WHO) histological subtype. Fifty-three percent were female and the mean age was 71. The upper jaw (maxilla or palatal bone), mandible, palatal soft tissue, and vestibule and gingivae (maxillary or mandibular soft tissue involvement only) were, respectively, the most common locations. Swelling, ulceration, and radiographic destruction of bone were the most frequent signs. Most of the lymphomas were of B cell lineage (98%), and the majority of these B cell lymphomas (58%) were histologically subtyped as diffuse large B cell lymphoma, which is considered to have an aggressive clinical course. An immunohistochemical panel was used in the majority of cases to confirm the lineage and to help characterize the subtype. B and T cell specific markers were used to show lineage of the neoplastic cells. Additional markers were used to help confirm specific subtypes that characteristically show specific positivity to some of these antibodies. Molecular studies to detect monoclonal immunoglobulin heavy chain (IgH) gene rearrangements and Bcl-1 and Bcl-2 gene translocations were performed in cases in which the diagnosis was in question. The current WHO classification is also reviewed in detail.
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PMID:Oral non-Hodgkin's lymphoma: review of the literature and World Health Organization classification with reference to 40 cases. 1760 60


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