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)

In order to improve the cytomorphologic diagnosis of malignant lymphoma on lymph node fine-needle aspiration (FNA), and to make a confident discrimination between low-grade follicular non-Hodgkin's lymphoma (NHL) and lymphoid hyperplasia, polymerase chain reaction (PCR) analysis was performed of the Ig CDR3 region and BCL2 breakpoint region in 25 nonselected cases of malignant lymphoma (17 NHL and 8 Hodgkin's disease [HD]) with histologic control, and 22 cases of lymph nodal hyperplasia with histologic and/or clinical control. Among lymphomas, IgH monoclonality was detected in 7 (77%) of 9 NHLs and BCL2 rearrangement in 3 (17.6%) of 17 NHLs, all of which were follicular centroblastic-centrocytic (FCBCC). Three BCL2/JH negative FCBCC cases were monoclonal for CDR3. Neither IgH monoclonality nor BCL2 rearrangement were found in HD. Among cytologically diagnosed lymphoid hyperplasias, one IgH polyclonal case was considered false-negative, being histologically diagnosed as lymphoplasmacytic NHL on the subsequent excisional biopsy. Another 4 cases (2 BCL2 rearranged and 2 monoclonal for IgH) were considered false-positive on the basis of histologic features or clinical control. These data indicate that the combined PCR analysis of IgH and BCL2 rearrangements can confirm a cytologic diagnosis of lymphoma in FNAs while, due to the occurrence of both false-positive and false-negative results, it is of limited value in the distinction between follicular lymphoma and lymphoid hyperplasia without morphologic or clinical support.
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PMID:PCR analysis of IgH and BCL2 gene rearrangement in the diagnosis of follicular lymphoma in lymph node fine-needle aspiration. A critical appraisal. 927 87

The pediatric Non-Hodgkin's lymphomas are a heterogeneous group of malignancies of B- or T-cell origin. Approximately half of them are characterized as Burkitt's lymphomas. Typically, one of the reciprocal translocations t(8;14)(q24;q32), t(2;8)(p11;q24) or t(8;22)(q24;q11) is seen in the tumor cell, each involving the protooncogene c-myc on chromosome 8. Characteristically, in most patients the translocation occurs between the distal end of the long arm on chromosome 8 (c-myc) and chromosome 14 (immunoglobulin heavy chain locus, IgH). The breakpoint regions are distributed over a wide range of more than 10 Kb on chr. 8 and over several hundred Kb on chr. 14. With standard-PCR, fragments can only be amplified to a size of about 2 Kb. The development of PCR-applications to generate long products up to 20 Kb now allows a detection of these breakpoints. Several primer pairs from different regions of the IgH-gene and the c-myc-gene were tested in each patient. Until now, 20 patients with Burkitt's Lymphoma or B-ALL characterized by L3 morphology were examined. All patients were treated according the protocols of the NHL-BFM '90 or '95 study. In 11/20 patients, recombinations between chromosomes 8 and 14 could be detected with our primer pairs. In serial dilutions of DNA from malignant cells in DNA from healthy controls, sensitivities of one malignant cell in 2 x 10(4) normal cells could be obtained. This method will now allow us to characterize the involved breakpoints more exactly and to analyze patient samples (blood, bone marrow, aphereses products and residual tumors) during or after therapy for the existence of minimal residual tumor cells.
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PMID:[Detection of translocation t(8;14)(q24;132) in pediatric Burkitt's lymphomas using "long distance" polymerase chain reaction: a new method for diagnosis of Burkitt's lymphomas]. 934 Apr 26

We investigated 44 cases of Hodgkin's disease for Epstein-Barr virus genome with EBER-1 in situ hybridization. Twenty of 44 (45.5%) were positive for EBV. Simultaneously, immunoglobulin gene rearrangements were assessed in 32 of these 44 cases with PCR on DNA extracted from Reed-Sternberg cell (RS-cell) -rich areas microdissected from paraffin sections. Clonally rearranged immunoglobulin (IgH) gene was observed in 15 cases (46.9%). EBV-negative cases showed more frequent IgH rearrangement than EBV-positive cases (10 and 5 cases, respectively). In 9 cases, the RS cells were CD20-positive immunohistochemically and these were all EBV negative and the IgH gene was rearranged in all except one. These findings may suggest that EBV infection has occurred before the immunoglobulin gene rearrangement or that EBV infection has influenced the rearrangement of the immunoglobulin gene. The results may also hint towards the obscure B-cell nature of the RS cells.
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PMID:Reappraisal of the relationship between immunoglobulin heavy chain gene rearrangement and Epstein-Barr virus infection in Reed-Sternberg cells of Hodgkin's disease. 949 13

Subclassification of malignant non-Hodgkin's lymphoma is important to be able to choose the right treatment. However, this subclassification can be difficult, and immunohistochemistry and polymerase chain reaction are used to improve diagnostic safety. We have investigated the value of immunohistochemistry and polymerase chain reaction in the subclassification of 49 low grade non-Hodgkin's lymphomas of B-cell type. Immunohistochemistry showed B-cell phenotype in all biopsies, and 23 (85%) of 27 follicular lymphomas showed positive reaction for bcl-2 antibodies in follicles. Polymerase chain reaction demonstrated a monoclonal pattern for IgH in 36 (73%) of 49 biopsies, and 10 (37%) of 27 follicular lymphomas demonstrated translocation (14; 18). Immunohistochemistry and polymerase chain reaction contributed to subclassification or confirmation of the diagnosis of 46 (94%) of 49 biopsies. Our conclusion is that immunohistochemistry and polymerase chain reaction have a natural place in the diagnosis of lymphomas.
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PMID:[Low grade non-Hodgkin lymphoma of B-cell type. What is the benefit of polymerase chain reaction and immunohistochemical examination?]. 949 31

Relationship and histogenesis of Hodgkin's disease (HD) and anaplastic large cell lymphoma (ALCL) still remain unclear. Recently, Reed-Sternberg cells or Hodgkin cells in HD with B cell phenotype (B-HD) are considered to originate from germinal center B cells, ALCLs of B cell phenotype (B-ALCL) are involved in diffuse large B cell lymphoma (DLBCL) as anaplastic variant, but an origin of tumor cells of B-ALCL has not been elucidated. We have therefore investigated somatic mutation of the lg heavy chain (IgH) genes among 17 cases of B-ALCL to clarify whether there is a difference in characteristic and origin of tumor cells between B-ALCL, B-HD and DLBCL. Amplificates of IgH variable (V) region of 10 cases by the polymerase chain reaction method were sequenced and compared with reported germ line configurations. Nine cases (90%) with heavily somatic mutations were found. A case with an out-of-frame rearrangement and a case with 9 base pairs insertion were included. The mutation pattern revealed the tumor cells were selected for antibody expression and discriminated from B-HD. These findings suggest the tumor cells of B-ALCL are derived from germinal center or postgerminal center (memory and effector) B cells and an origin of B-ALCL is not different from DLBCL.
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PMID:Most of CD30+ anaplastic large cell lymphoma of B cell type show a somatic mutation in the IgH V region genes. 959 74

The use of allogeneic BMT in patients with relapsed non-Hodgkin lymphoma (NHL) offers the advantage of tumor-free bone marrow and possibly a 'graft-versus-lymphoma effect' which may decrease the risk of recurrence. However, allogeneic BMT also poses an increased risk of death due to graft-versus-host disease (GVHD) which can be ameliorated by T cell depletion. We performed a retrospective review of 37 patients who underwent T cell-depleted allogeneic BMT for aggressive and indolent NHL between 1988 and 1996. Polymerase chain reaction (PCR) was used to identify indolent NHL patients with the BCL2/IgH translocation which served as a marker of residual disease. Sixteen of 37 patients (44%) are alive and progression-free with a median follow-up of 4.4 years (range 1-10.3). The incidence of grade 2-4 acute GVHD was 36% and extensive chronic GVHD developed in 12%. Patients with aggressive NHL have an overall PFS of 33% (12-54%); those with chemotherapy-resistant and sensitive disease have PFS of 17% (0-47%), and 40% (15-65%) respectively at 5 years. Patients with indolent histologies have overall PFS of 62% (37-86%); those with chemotherapy-resistant and sensitive disease have PFS of 55% (25-85%) and 80% (45-100%) respectively at 5 years. Eight patients with indolent disease had a BCL2/IgH translocation detectable by PCR. Five of these eight patients remain alive and progression free at a median of 6.5 years after BMT (range 2.1-7.4 years), four of whom remain PCR positive from 1.7 to 2.9 years after transplantation. We conclude that T cell-depleted allogeneic BMT poses a low risk for death due to GVHD, and should be considered for patients with relapsed and refractory indolent NHL.
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PMID:T cell-depleted allogeneic bone marrow transplantation for high-risk non-Hodgkin's lymphoma: clinical and molecular follow-up. 961 81

Non-Hodgkin's B-lymphomas (B-NHL) are a very heterogeneous group of B-cell neoplasias originating from the germinal centers of lymphatic follicles. Thus, they represent a suitable experimental model to study the molecular basis of certain key events which take place in the lymphatic follicles, including somatic hypermutation and heavy chain isotypic switch. An unusual B-NHL cell line ("Farage") not producing Ig polypeptide chains was previously shown to rearrange its IgH and Igkappa genes and transcribe seemingly normal size mu and kappa mRNAs. In an attempt to characterize the phenotype of Farage cells better and to elucidate the molecular basis of the failure of Farage cells to synthesize Ig chains, we sequenced its VH and Vkappa rearranged gene segments by PCR and RT-PCR. It was found that both V genes are somatically, heavily mutated compared to their germline counterparts. In addition, this rearranged VDJ gene of the heavy chain is not transcribed. Instead, the Farage cells express a low level of a new family of germline transcripts starting with a VH like sequence, continuing with a small segment of the 3'VH germline flanking region, and ending within the Cmu region. These transcripts lack D and J segments and do not contain the open reading frame of the full-length Cmu protein. Thus, Farage cells fail to produce mu heavy chains due to silencing of the expression of the conventional VDJCmu transcript and expression of unusual Cmu-germline transcripts. In contrast to the IgH genes, the rearranged VJ gene of Farage is transcribed and gives rise to a full-size kappa-mRNA. This transcript, however, is not translated to a full-length kappa-chain, as it contains a stop codon in its coding region. All the above show that Farage cells are unable to produce Ig polypeptide chains, due to somatic mutations altering the kappa-chain gene, and mutations and/or regulatory events that shutoff the transcription of the IgH gene. The heavily mutated Vkappa and Vkappa genes found, support the conclusion that the Farage cell line originated either from germinal center cells or from the mantle zone of the lymphoid follicle.
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PMID:Somatic mutations in the Ig variable region genes and expression of novel Cmu-germline transcripts in a B-lymphoma cell line ("Farage") not producing Ig polypeptide chains. 971 26

We report 2 cases of agranular CD2- CD4+ CD56+ non-Hodgkin lymphoma in which skin seemed to be the primary site. A 21-year-old woman's initial symptom was a skin nodule on the right cheek. She also had tumors in the nasopharynx, and the bone marrow subsequently became involved. No lymphadenopathy was present. She experienced complete remission after dose-intensified therapy with cyclophosphamide, hydroxydaunomycin, vincristine [Oncovin], and prednisone (CHOP), but the disease relapsed in the central nervous system 6 months later. An 81-year-old man experienced an 11-month history of skin nodules in the left forearm. On admission, he had a bone marrow infiltration of lymphoma cells. He died of pneumonia during chemotherapy. The malignant cells of the 2 patients had similar morphologic features, with a monocytoid nucleus and no cytoplasmic granules. The cells in both cases showed a unique phenotype: CD2-, CD3-, CD4+, CD8-, CD13-, CD14-, CD34-, CD16-, CD56+, CD57-, HLA-DR-positive. Staining for peroxidase and alpha-naphthyl butyrate esterase was negative. The T-cell receptor beta, gamma, delta, IgH, kappa, lambda genes were of germ line configurations. The DNA of Epstein-Barr virus was not detected from the bone marrow cells by polymerase chain reaction. Only 3 other cases with similar phenotypes have been reported; all had skin lesions. Although the origin of these cells remains unknown, we propose that this is a distinct clinicopathologic entity.
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PMID:A cutaneous agranular CD2- CD4+ CD56+ "lymphoma": report of two cases and review of the literature. 1043 11

Hodgkin's disease (HD) represents a malignant lymphoma in which the putative malignant Hodgkin and Reed-Sternberg (H-RS) cells are rare and surrounded by abundant reactive cells. Single-cell analyses showed that H-RS cells regularly bear clonal Ig gene rearrangements. However, there is little information on the clinical evolution of HD in a given patient. In this study, we used the single-cell polymerase chain reaction (PCR) to identify H-RS cells with clonal Ig gene rearrangements in biopsy specimens of patients with relapsed HD. The obtained clonal variable region heavy-chain (VH) gene rearrangements were used to construct tumor-clone-specific oligonucleotides spanning the complementarity determining region (CDR) III and somatically mutated areas in the rearranged VH gene. A number of biopsies were obtained during a period of 3 years from two HD patients. H-RS cells with identical VH rearrangements were detected in two separate infiltrated lymph nodes from one patient with nodular sclerosis HD. In a second patient with mixed cellularity HD subtype, clonal VH rearrangements with identical sequences were detected in infiltrated spleen and two lymph node biopsies. Despite the high sensitivity of the PCR method used (one clonal cell in 10(5) mononuclear cells), residual H-RS cells were not found in peripheral blood, leukapheresis material, purified CD34(+) stem cells or bone marrow. The results show that different specimens from relapsed patients suffering from classical HD carry the same clonotypic IgH rearrangements with identical somatic mutations, demonstrating the persistence and the dissemination of a clonal tumor cell population. Thus, PCR assays with CDRIII-specific probes derived from clonal H-RS cells are of clinical importance in monitoring the dissemination of HD and tumor progression and could be useful for analysis of minimal residual disease after autologous stem cell transplantation.
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PMID:Detection of clonal Hodgkin and Reed-Sternberg cells with identical somatically mutated and rearranged VH genes in different biopsies in relapsed Hodgkin's disease. 976 76

Recently, single-cell PCR studies have demonstrated that Hodgkin and Reed-Sternberg (HRS) cells are clonally related in many cases of Hodgkin disease. To investigate the lineage and clonality of neoplastic cells in local environments in nodular sclerosis Hodgkin disease (NSHD), we microdissected multiple distinct nodules from patients with NSHD and analyzed them for IgH gene rearrangement by PCR. These results were correlated with immunophenotype, Epstein-Barr-encoded RNA (EBER) expression, and clinical outcome. Forty individual nodules from 10 patients with NSHD (11 specimens) were microdissected from formalin-fixed paraffin-embedded tissue. DNA extracts were analyzed for IgH gene rearrangement by using PCR with FRIIIa and JHa primers. Cases were immunophenotyped in paraffin sections with antibodies to CD20(L26), CD79a(HM57), CD45RO(A6), CD15 (Leu-M1), and CD30(Ber-H2). Infection of HRS cells by Epstein-Barr virus was evaluated by using EBER in situ hybridization (EBER-ISH). DNA extracts from 12 of 40 microdissected nodules from 8 of 10 patients demonstrated a monoclonal pattern by IgH-PCR. Three patients demonstrated 2 individual nodules with different monoclonal patterns. One patient demonstrated 2 nodules with bands that appeared similar in size but were found to be different from one another upon further testing. All 28 remaining nodules demonstrated a polyclonal pattern. Six of 10 patients were positive for the Epstein-Barr virus genome by EBER-ISH. No correlation was found between IgH monoclonality, immunophenotypic features, Epstein-Barr virus infection, or clinical outcome. It was concluded that a subset of NSHD cases contain detectable monoclonality within individual nodules by IgH-PCR, suggesting that HRS cells are clonally related within local microenvironments.
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PMID:Monoclonal IgH gene rearrangement in microdissected nodules from nodular sclerosis Hodgkin disease. 980 44


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