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 excellent results in pediatric lymphomas presented at the Sixth International Conference on Malignant Lymphoma in Lugano encompass several emerging themes and provide paradigms which it may be possible to extrapolate to at least some adult lymphomas. In pediatric Hodgkin's disease, there is mounting evidence that radiation adds nothing except toxicity to effective chemotherapy regimens, with the possible exception that patients with bulky disease, particularly in the mediastinum, may benefit from involved-field radiation. This is of particular importance in view of the recently recognized high rate of late-occurring second solid tumors and cardiac infarction, largely referable to radiotherapy. It is likely that there will be greater efforts to eliminate radiation from treatment protocols wherever possible. In pediatric non-Hodgkin's lymphomas, the intensive regimens used by several cooperative groups in Europe and the United States have resulted in very high event-free survival rates--90% in B-cell lymphomas, and only slightly lower in T-cell lymphomas. These results stand in striking contrast to those obtained in adults with the same diseases, except those treated with the same treatment protocols, who appear to have a similar prognosis. Finally, progress in the characterization of the molecular abnormalities and viral association of pediatric lymphomas is leading to new approaches to diagnosis and the detection of minimal residual disease, as well as to the development of targeted treatment approaches.
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PMID:The treatment of pediatric lymphomas: paradigms to plagiarize? 918 22

Several methods have been developed for the detection of minimal residual disease (MRD) in B cell tumors. Chromosomal translocations or the rearrangement of the immunoglobulin heavy chain (IgH) and T cell receptor genes are generally employed. We report a novel PCR method to detect MRD using IgH genes. IgH rearranged variable region (VDJ) were amplified from tumor specimens using consensus primers for variable and joining region genes. Complementarity-determining regions (CDR) were identified and used to generate tumor-specific primers. Two-round amplifications using primers derived from CDRs and joining or constant regions were performed for MRD detection. IgH nested-PCR approach was tested on a panel of 75 B cell tumors including acute lymphoblastic and chronic lymphocytic leukemias, non-Hodgkin's lymphomas and multiple myelomas. A VDJ sequence was obtained in 62 out of 75 cases (83%). Sensitivity using DNA or cDNA templates was 10(-5) and (-6), respectively. This method is specific and sensitive and provides a simple, non-radioactive approach for the evaluation of MRD in B cell tumors.
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PMID:A novel nested-PCR strategy for the detection of rearranged immunoglobulin heavy-chain genes in B cell tumors. 932 3

We measured the soluble IL-2 receptor alpha (sIL-2R alpha) in sera and in bone marrow of 20 patients with minimal residual hematological malignances, 6 of them with multiple myeloma (MM), 8 with Hodgkin's disease (HD) and 6 with non-Hodgkin's lymphoma (NHL), low grade. Compared to 10 normal individuals, HD and NHL group of patients had in sera significantly increased levels of sIL-2R alpha (252.8 +/- 42.9 versus 1437.2 +/- 1639 and 761.8 +/- 431 U/ml, respectively). After low-dose IL-2 given subcutaneously once daily at a dose of 1.8 x 10(6) U/patient for 3 weeks, additional significant increase in levels of IL-2R alpha was observed in sera and in bone marrow of patients with NHL (761.8 +/- 431 versus 2633 +/- 788 U/ml and 785 +/- 448 versus 2475 +/- 431 U/ml, respectively). The increase of sIL-2R alpha level after IL-2 therapy was also seen in sera and in bone marrow of HD and MM group; however, because of high standard deviation this increase was not statistically significant. We conclude that 1) in comparison to healthy subjects the levels of sIL-2R alpha remained elevated in HD and NHL patients, even at the stage of minimal residual disease (MRD) after intensive chemotherapy or radiotherapy, 2) the levels of sIL-2R alpha which appeared in sera and bone marrow of patients after IL-2 therapy seemed to be dependent on the type of hematological disorders.
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PMID:Detection of soluble IL-2 receptor in the serum and bone marrow of patients with minimal residual hematological malignancies: induction under therapy with IL-2. 943

Monoclonal antibodies coupled to drugs and toxic agents (immunotoxins) or radionuclides (radioimmunoconjugates) represent new tools for immunotherapy of haematological malignancies. Immunotoxins constructed with toxins of either plant or bacterial origin have shown a powerful antitumor activity both in vitro and in mice with severe combined immunodeficiency bearing various kinds of leukaemias and lymphomas. Preliminary clinical trials have shown an activity of these compounds at least in a proportion of patients. However, tumour responses have generally been partial and transient. The main problems with immunotoxin therapy remain the inability of immunotoxins to target tumour cells in the presence of a high burden of disease, the host immune response against both the antibody and the toxin moieties, which precludes repeated administration of immunotoxins, and the vascular leak syndrome. Targeting of tumour cells with specific antibodies armed with radionuclides (usually iodine-131 or yttrium-90) appears to be an even more attractive approach. Preliminary clinical studies have clearly demonstrated the ability of radioimmunoconjugates, especially when administered at high dose followed by bone marrow rescue, to induce durable complete remission in patients with non-Hodgkin's lymphomas refractory to conventional therapies. Radioimmunotherapy also overcomes the antigenic heterogeneity of the tumour cell population, since antigen negative tumour cells will be irradiated by the nearby targeted antigen-positive cells. Efforts should now be focused on defining more precisely the optimal clinical setting for administration of immunotoxin and radioimmunoconjugates (e.g. minimal residual disease), to reduce the immunogenicity of these compounds and solve the problem of vascular leak syndrome.
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PMID:Targeted antibodies in the treatment of lymphomas. 954 98

The theoretical basis of cancer vaccination having been well established during the past two decades, the translation of this knowledge into clinically applicable immunisation procedures is now an urgent need. Numerous antigenic preparations are available that are capable of inducing specific anti-tumour immunity which can be augmented by appropriate cytokines. Promising tumour vaccination results have been obtained in B-cell malignancies, colorectal carcinoma, and melanoma; tumour regression has been noted in myeloma, non-Hodgkin lymphoma, colorectal carcinoma, and melanoma patients, and significantly prolonged disease-freed survival in non-Hodgkin lymphoma and colorectal carcinoma patients. The presence of only minimal residual disease would seem to be a clinical prerequisite for tumour vaccination.
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PMID:[Vaccination against cancer soon a therapeutic possibility. B-cell tumors, colonic cancer and melanoma may be suitable for this treatment]. 956 Sep 67

Low grade B-cell non-Hodgkin's lymphomas (B-NHL) represent a markedly heterogeneous group of lymphoproliferative disorders, including B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma (B-CCL/SLL), lymphoplasmacytoid lymphoma (LPL), follicular lymphoma (FL), mucosa-associated lymphoid tissue lymphoma (MALTL), and splenic lymphoma with villous lymphocytes (SLVL). The molecular pathogenesis of low grade B-NHL is characterized by distinct genetic pathways which selectively associate with each clinicopathologic category. At diagnosis, B-CLL/SLL frequently display deletions of 13q14 and trisomy 12, whereas evolution to Richter's syndrome associates with disruption of p53. LPL carries t(9;14)(p13;q32) in 40-50% of the cases, leading to the deregulated expression of the PAX-5 gene. FL consistently harbors rearrangements of BCL-2 independent of the cytologic variant. With time, a fraction of FL cases accumulates mutations of p53 and evolves into a high grade B-NHL. Low grade MALTL are characterized by the frequent occurrence of trisomy 3 and, occasionally, by p53 mutations. SLVL carries p53 mutations in a fraction of cases. The identification of distinct genetic categories among low grade B-NHL may help in the therapeutic stratification of these disorders. In addition, genetic lesions of low grade B-NHL have proved to be a useful molecular marker for monitoring minimal residual disease.
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PMID:Molecular pathways in low grade B-cell lymphoma. 957 Jun 87

Anaplastic large cell lymphoma (ALCL) is an intermediate grade Non-Hodgkin's lymphoma (NHL) characterized by the frequent presence of the t(2;5)(p23;q35). This translocation fuses the nucleophosmin (NPM) gene on chromosome 5q35 to a protein kinase gene (Anaplastic Lymphoma Kinase, ALK) on chromosome 2p23. In order to determine the frequency of t(2;5) we used a DNA polymerase chain reaction (PCR) amplification using genomic DNA, 5'-primers derived from the NPM gene, and 3'-primers derived from the ALK gene. The presence of amplifiable DNA in the samples was established with PCR and oligonucleotide primers designed to amplify a 3,016 bp fragment from the beta-globin locus. The t(2;5) PCR assay was established using DNA isolated from three t(2;5)-positive ALCL cell lines. Its ability to amplify genomic DNA prepared for routine molecular diagnostic use was validated using archival DNA from four ALCL tumors known to be t(2;5)-positive. Its sensitivity was established by serially diluting t(2;5)-positive DNA in normal DNA: amplicons were generated in 100% of reactions diluted 10(4)-fold (6-8 cells per tube) and in 30% of those diluted 10(5)-fold (0.6-0.8 cells per tube.) We subsequently analyzed archival genomic DNA extracted from 38 ALCL, 77 NHLs, 37 Hodgkin's lymphomas, and 9 lymphomatoid papuloses. The t(2;5) was detected in 6 ALCLs (16%, 95% confidence intervals 6%-31%), but not in any other lymphoma, or in lymphomatoid papulosis. By using the published sequence of the fourth NPM intron that is involved in t(2;5) and by sequencing the individual tumor amplicons and also the normal ALK intron that is involved in t(2;5), we established that all breakpoints involve the same introns in the ALK and NPM loci. Detailed analysis demonstrated that each translocation generates a unique breakpoint sequence, and suggested that sequence homology between the ALK and NPM intron sequences may be involved in the translocation. We conclude that genomic DNA-PCR is useful for the detection of t(2;5) that in our patient population is restricted to ALCL and is not detectable in other NHL, Hodgkin's disease, or lymphomatoid papulosis. More work is needed to determine the prognostic significance of t(2;5), and to establish the utility of the genomic DNA PCR in monitoring minimal residual disease.
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PMID:Genomic DNA amplification and the detection of t(2;5)(p23;q35) in lymphoid neoplasms. 964 64

The exonuclease-based real-time polymerase chain reaction (PCR) exploits 5'-->3' exonuclease activity of Taq polymerase and measures PCR product accumulation as the reaction proceeds through a dual-labeled fluorogenic probe. The utility of this exonuclease-based PCR assay as a rapid alternative to conventional PCR for follicular lymphoma-associated t(14;18)(q32;q21) was evaluated in this study. The specificity of the assay for t(14;18) involving bcl-2 and immunoglobulin heavy-chain joining region (JH) genes was assessed by analyzing DNA from 53 patients (38 B-cell non-Hodgkin's lymphomas and 15 nonneoplastic proliferations) and correlating the exonuclease PCR data with conventional PCR results. bcl-2/JH fusion sequences were detected by exonuclease-based PCR in 24 of 25 cases shown to be bcl-2 rearranged by conventional PCR. Fusion sequences were not detected in patients who were negative by conventional PCR. The overall concordance between the two assays was 98% (52 of 53 cases concordant positive or negative). In a serial dilution study using t(14;18)-positive cell line DNA, exonuclease-based PCR detected fusion sequences at DNA concentrations of 5 pg, equivalent to 0.6 to 0.8 genomes per reaction. Thus, this study demonstrated that exonuclease-based PCR for t(14;18) is both specific and highly sensitive. The elimination of the post-PCR amplicon detection steps and the ability to quantitate the input target DNA sequences make this assay ideal for routine diagnostics and monitoring minimal residual disease.
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PMID:Novel 5' exonuclease-based real-time PCR assay for the detection of t(14;18)(q32;q21) in patients with follicular lymphoma. 966 66

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

Follicular lymphoma constitutes 30-40% of non-Hodgkin's lymphomas. Most patients have widespread disease at diagnosis. The clinical course is generally indolent, and it is not usually curable with available treatment. The source of relapse in patients who achieve complete clinical remission is residual neoplastic cells that are present below the limits of detection using standard techniques. With the development of PCR technology, the presence of these residual malignant cells [Minimal Residual Disease (MRD)] has been demonstrated clearly. Recently, an association of high-dose chemotherapy with autologous bone marrow or peripheral blood progenitor cell autograft appeared promising in the treatment of these lymphomas. In the search of clonal markers for the detection of MRD in follicular lymphomas, two strategies can be used. In the cases associated with the t(14;18) (q32;q21) chromosomal translocation, the bcl-2/JH junctional regions are amplified by PCR in approximately equal to 50% of cases and then sequenced in order to synthesize an anti-junction oligonucleotide probe specific for each patient's malignant clone (clonospecific probe). In the cases negative for this translocation, an alternative strategy consists in the amplification of immunoglobulin high chain (IgH) gene rearrangement (approximately equal to 75% of cases). The present review highlights the value of molecular markers such as bcl-2/JH and VH/JH rearrangements to follow the neoplastic clone and to detect MRD in patients with follicular lymphomas.
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PMID:[Detection of residual disease in follicular lymphomas using the PCR technique: importance of clono-specific probes]. 983 62


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