UNIPROT:Q06643 - FACTA Search

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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 clinico-pathological study was carried out in 21 cases of primary central nervous system-non-Hodgkin's lymphoma (CNS-NHL). Their clinical profiles (age, prognosis, modalities of treatment) and findings of radio-imaging were analyzed. All specimens from surgery and/or autopsy were histologically classified according to the working formulation (WF) classification of the National Cancer Institute. Ontogeny of lymphoma cells was determined by immunohistochemical study in all cases and some cases were subjected to light (kappa, lambda) and heavy chain (IgG, IgA, IgM) analysis as well. Among 21 cases, 12 cases were located in the cerebral hemisphere, 7 in the thalamus-basal ganglia and 4 in the cerebellum. Radio-imaging study showed that 18 cases (86%) revealed isodensity mass lesions on plain CT, which were homogeneously enhanced by contrast medium. The pathological study showed that all cases were derived from B-cells. Five were classified as immunoblastic type (IBL), 9 as diffuse large type (DL), and the others were classified according to WF. 17 of 21 cases (81%) were sensitive to radiotherapy, and 15 of 19 cases (79%) responded to corticosteroid. A prognostic study revealed that patients with IBL had less hope than those with DL. From this result, it seems that WF classification is better than LSG classification for obtaining a prognosis in malignant lymphoma patients. The frequency of primary CNS-NHL has been increasing for the past several decades and will surpass that of any other brain tumors in the near future because of the explosive expansion of AIDS patients. Therefore, not only clinicopathological analysis but also biological study for CNS-NHL might be important.
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PMID:[A clinicopathological study of 21 cases of primary central nervous system lymphoma]. 809 Feb 64

Partner sites of 14q32 translocations found in B-cell malignancies were detected by fluorescence in situ hybridization (FISH) using yeast artificial chromosome (YAC) clones, Y20 and Y6, containing the human Ig heavy chain (IgH) gene locus. Y20 spans a 160-kb upstream and 40-kb downstream region of the JH segments on chromosome band 14q32.33. Y6 is 300-kb upstream of Y20, and spans a further 320-kb telomeric region. The human DNA sequences amplified by Alu polymerase chain reaction of the YAC clones were used as probes for FISH to study six patients with non-Hodgkin's lymphoma (NHL), one patient with acute lymphoblastic leukemia, and one cell line FR4 established from a plasmacytoma. Three telomeric YAC clones each specific for 3q, 8q, and 18q were also used to further characterize 14q32 translocations. The IgH YACs were successfully applied to detect cytogenetically invisible subtelomeric translocation of the IgH gene locus to each partner site in t(14;18), t(8;14), and t(14;19), and to identify t(3;14) (q27;q32.33) in three patients with 14q32 translocation of unknown origin. Furthermore, complex translocations involving more than three chromosomes were detected in an NHL patient with t(8;14), and t(3;12), and in the FR4 with der(14)t(8;14), der(8)dic(1;8), and del(1)(q21). The technique would be a useful tool in elucidating the mechanisms of a 14q32 translocation in B-cell malignancies.
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PMID:Detection of 14q32 translocations in B-cell malignancies by in situ hybridization with yeast artificial chromosome clones containing the human IgH gene locus. 818 Mar 92

Seminested polymerase chain reaction (PCR) was used to amplify the DNA fragments of the complementarity-determining region 3 of the immunoglobulin (Ig) gene heavy chain from the malignant cell specimens of patients with leukemias and lymphomas of B-cell lineage. Two different pairs of primers were used sequentially. Twenty of the 27 (74%) acute lymphoblastic leukemia (ALL) patients, 14 of 19 (74%) chronic lymphocytic leukemia (CLL) patients and eight of 20 (40%) non-Hodgkin's lymphoma (NHL) patients, who had rearrangement of the Ig gene heavy chain by Southern analysis, were positive by the seminested PCR. False-negative results appeared to occur more commonly in cases of lymphoma. The PCR analysis was also less likely to be positive if one-stage PCR studies with either pair of primers were both negative. The seminested PCR technique was found to have a high sensitivity of detecting malignant cells at the level of 0.02%. The clinical application of this assay needs to be investigated further.
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PMID:Detection of immunoglobulin gene rearrangement in lymphoid malignancies of B-cell lineage by seminested polymerase chain reaction gene amplification. 831 59

A method was established to detect clonal B cell populations in frozen and paraffin-embedded tissues. The method is based on the polymerase chain reaction amplification of rearranged VH and V kappa genes using V gene family-specific primers. Monoclonal B cell populations could be detected in peripheral blood lymphocyte DNA in all 16 cases of B-CLL and immunocytoma investigated and in 8 of 10 cases of B cell non-Hodgkin's lymphoma using frozen and paraffin sections. The amplification of V kappa rearrangements in addition to the VH amplification is a useful tool to verify the results of the heavy chain rearrangement and to detect proliferation of a B cell clone in cases in which no VH product was obtained. In spite of the degradation of DNA in paraffin-embedded tissues, we were able to find amplified polymerase chain reaction products of about 350 bp length in 8 of 10 cases analyzed. The method presented here may be helpful in routine diagnosis of B cell non-Hodgkin's lymphoma using frozen or paraffin-embedded specimens.
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PMID:Detection of clonal B cell populations in paraffin-embedded tissues by polymerase chain reaction. 831 49

Rearrangement of the BCL2 gene with the immunoglobulin (IG) genes is the most frequent genetic abnormality in B cell lymphoid neoplasms. In the majority of cases, breakages occur at two breakpoint cluster regions; major breakpoint cluster (MBR) and minor cluster region (mcr). In a minority of cases with non-Hodgkin's lymphoma (NHL) and chronic lymphocytic leukemia (CLL), rearrangements involving the 5' flanking region of the BCL2 (5'-BCL2) have been reported. Here, we investigated 196 patients with NHL and 31 with CLL, with regard to rearrangement of the BCL2 gene. Hybridization analyses using probes representing the three cluster regions revealed that a total of 57 patients had a rearrangement of the BCL2; 42 (73.7%) were within the MBR, seven (12.2%) were within the mcr, and nine (15.8%) had a rearrangement at the 5'-BCL2. The nine patients with 5'BCL2 rearrangement included two with follicular lymphoma, four with diffuse large cell lymphoma and immunoblastic variant, two with leukemic phase of follicular lymphoma, and one with CLL. Comigration analysis with probes for the IG heavy chain gene (IGH), kappa-chain gene (IG kappa) and lambda-chain gene (IG lambda), demonstrated a 5'-BCL2/IGH junction at the JH region in four patients with NHL derived from follicular center B cell. Thus, the 5'flanking region is a third cluster for recombination between the BCL2 and IGH, which is closely associated with the development of follicular center cell lymphoma. Molecular cloning of a 5'-BCL2/IGH junction demonstrated recombination of the two affected genes in divergent orientation. A 5'-BCL2/IG kappa junction was observed in two patients with immunoblastic lymphoma, and one with CLL had a 5'-BCL2/IG lambda recombination. Two patients, including one with a BCL2-MBR/JH junction, lacked obvious recombination of the 5'-BCL2 with IG genes, suggesting the presence of a deletion at the 5'-BCL2. Our findings demonstrated heterogeneity not only in clinicopathological presentation of B cell disease with rearrangement of 5'-BCL2, but also in molecular lesions resulting from the rearrangement.
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PMID:Rearrangement of the 5' cluster region of the BCL2 gene in lymphoid neoplasm: a summary of nine cases. 866 54

It was the aim of this study to examine the prognostic value of the detection of minimal residual disease (MRD), with the help of the polymerase chain reaction (PCR), in patients with non-Hodgkin's lymphoma (NHL) and multiple myeloma (MM) who underwent sequential high-dose therapy with peripheral blood progenitor cell (PBPC) support, and in patients with acute myeloid leukemia (AML) of the subclass M4Eo who underwent high-dose consolidation therapy. Basis for the application of a PCR assay in these disease entities are the following specific gene rearrangements: the t(14;18) translocation in a high percentage of NHL, the clonal rearrangement of the Ig heavy chain locus resulting in a unique complementary determining region 3 (CDR3) for MM region and the inversion 16 characteristic for the M4Eo subclass of AML. Before the G-CSF-supported cytotoxic chemotherapy was given, 65% of the 52 patients with low- and intermediate-grade NHL enrolled into the study had PCR+ bone marrow (BM) and/or peripheral blood (PB) samples. The majority of patients (29 of 52) were autografted with a PCR+ transplant. The proportion of harvests containing t(14;18)+ cells was two-fold less in patients mobilized in first remission than in those with a history of previous treatment failure. This was also reflected when examining the B cell contents of the harvests measured as CD19+ cells with a 3.3-fold smaller proportion of CD19+ cells in leukapheresis (LP) products of patients mobilized in first remission. Patients who received a PCR- transplant are in remission and remained PCR- in BM and PB samples post-transplantation. Conversion to PCR-negativity in BM and PB samples post-transplantation was observed in 11 of 19 patients who were also in remission. In contrast, 6 of 29 patients who were autografted with PCR+ products relapsed, while 4 of them presented with PCR- samples on several occasions post-transplantation. In patients with MM, the assessment of MRD in PBPC harvests was based on the CDR3 regions of the Ig heavy chain locus as a marker for clonality. The great majority of LP products (17 out of 19) contained tumor cells. To prove positive enrichment procedures for the elimination of tumor cells, CD34+ and CD19+ cell fractions obtained from LP samples in an experimental setting via preparative flow cytometry were analyzed for MRD resulting in PCR-negativity for all CD34+ fractions. The results of the four patients with AML M4Eo and inversion 16 are preliminary, with a tendency of persistence of PCR-positivity after finishing the high-dose consolidation therapy. In one case, recurrence of disease was accompanied by an increase of the signal strength in the PCR assay. Longer follow-up periods are necessary to determine the prognostic value of these PCR findings in the different disease entities.
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PMID:Detection of minimal residual disease by polymerase chain reaction in B cell malignancies. 874 88

The t(9;14)(p13;q32) translocation is associated with approximately 50% of lymphoplasmacytoid lymphoma (LPL), a subtype of B-cell non-Hodgkin's lymphoma (NHL). We cloned the chromosomal breakpoint of der (14) from an LPL case (1052) and showed that it involved a junction between 9p13 and the switch micro region of the Ig heavy chain locus (IgH) on 14q32. Using a YAC contig spanning 1.5 megabase (Mb), we determined that the 9p13 breakpoint in one case (1052) mapped within a 270-kb restriction fragment containing two previously reported 9p breakpoints associated with a alpha-heavy chain disease case (MAL) and KI-1 positive diffuse large cell lymphoma (DLCL) cell line (KIS-1). The same fragment also contained the PAX-5 gene which encodes a B-cell specific transcription factor involved in the control of B-cell proliferation and differentiation. The breakpoints of KIS-1 and 1052 were mapped within the 5' noncoding region of PAX-5, while the 9p13 breakpoint of MAL mapped 230 to 270 kb upstream to PAX-5. In all three cases, the translocation caused the juxtaposition of the PAX-5 gene to the IgH locus in the opposite direction of transcription. When compared with six other DLCL cell lines lacking t(9;14)(p13;q32), the KIS-1 cell line showed an 11-fold overexpression of PAX-5 mRNA and a significantly reduced expression of the p53 gene, which is normally regulated by PAX-5. Moreover, metaphase and interphase fluorescence in situ hybridization (FISH) analysis using a YAC clone spanning 1 Mb including the PAX-5 as a probe identified chromosomal translocations in 5 of 7 cases carrying 9p13 translocations. These findings suggest that the PAX-5 gene is the target of the t(9;14) in LPL whereby its expression may be deregulated by juxtaposition to IgH regulatory elements, thus contributing to lymphomagenesis.
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PMID:The t(9;14)(p13;q32) chromosomal translocation associated with lymphoplasmacytoid lymphoma involves the PAX-5 gene. 894 44

Lymphotoxin-beta is a newly recognized member of the tumor necrosis factor ligand family. Recent studies have suggested a role for this cytokine in delayed-type hypersensitivity responses. To determine whether lymphotoxin-beta contributes to the development of contact sensitivity, we utilized an inhibitor protein that can effectively block binding of lymphotoxin-beta to its receptor. An adenoviral vector was created that encodes for a lymphotoxin-beta inhibitor protein consisting of the extracellular domain of the lymphotoxin-beta receptor fused to IgG heavy chain. Intravenous injection of the recombinant virus into BALB/c mice yielded plasma levels of inhibitor protein > 500 micrograms that persisted for 1 week. Mice treated in this manner were compared with control animals injected with adenovirus encoding beta-galactosidase, with respect to their ability to mount contact sensitivity responses to epicutaneously applied dinitro-fluorobenzene. Mice transduced with the lymphotoxin-beta inhibitor prior to the induction of contact sensitivity showed significantly suppressed ear swelling responses. By contrast, mice treated with the lymphotoxin-beta inhibitor prior to the elicitation of contact sensitivity showed no change in ear swelling responses in comparison to controls. These findings indicate that lymphotoxin-beta plays an important role in the afferent phase of the contact sensitivity response.
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PMID:Adenovirus-mediated blockade of lymphotoxin-beta inhibits the induction of contact sensitivity in mice. 929 89

Mantle cell lymphoma represent a clinicopathologically distinct entity of malignant non-Hodgkin's lymphoma (NHL) and are characterized by a specific chromosomal translocation t(11;14)(q13;q32) involving the cyclin D1 gene also designated as bcl-1/PRAD1 gene on chromosome 11 and the heavy chain immunoglobulin joining region on chromosome 14. We have established a PCR method to amplify t(11;14) junctional sequences in DNA from fresh frozen and paraffin-embedded tissue by bcl-1-specific primers in combination with a consensus immunoglobulin JH primer. A total of 65 cases histologically classified as mantle cell lymphoma (MCL) were analyzed for the presence of a t(11;14) translocation and monoclonal IgH-CDR3 rearrangements. From 26 patients with classical MCL and three cases with the anaplastic variant of MCL fresh frozen biopsy material was available for DNA extraction. We detected a bcl-1/JH rearrangement in 12 out of 29 samples (41%). In 36 cases paraffin-embedded lymph node tissue was the only source of DNA. In this material we found a bcl-1/JH rearrangement in six out of 31 samples with intact DNA (20%). To confirm the specificity of the PCR and to determine the bcl-1/JH junctional region sequences as clone-specific marker in individual patients we characterized the junctional DNA sequences by direct PCR sequencing in 16 cases. Interestingly we found that six bcl-1/JH junctions harbored DH segments in their N regions indicating that bcl-1/JH rearrangements can occur in a later stage of B cell ontogeny during which the complete VH to DH-JH joining or VH-replacement takes place. To investigate the suitability of IgH-CDR3 as sensitive molecular marker for those MCL patients in which a t(11;14) translocation can not easily be amplified, we additionally analysed 60 cases for the presence of monoclonally rearranged IgH genes by IgH-CDR3-PCR. A monoclonal IgH-CDR3 PCR product could be identified in 24 out of 29 fresh frozen samples (79%) whereas only 11 out of 31 samples (36%) with paraffin-derived DNA were positive. We demonstrate that automated fluorescence detection of monoclonal IgH-CDR3 PCR products allows the rapid and sensitive monitoring of minimal residual disease also in cases that lack a PCR amplifiable t(11;14) translocation. In combination with allele-specific primers the procedure may improve current experimental approaches for detection of occult MCL cells at initial staging and residual disease during and after therapy.
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PMID:Structure of Bcl-1 and IgH-CDR3 rearrangements as clonal markers in mantle cell lymphomas. 976 10

HOX11, a divergent homeodomain-containing transcription factor, was isolated from the breakpoint of the nonrandom t(10;14)(q24;q11) chromosome translocation found in human T cell acute lymphoblastic leukemias. The translocation places the HOX11 coding sequence under the transcriptional control of TCR alpha/delta regulatory elements, resulting in ectopic expression of a normal HOX11 protein in thymocytes. To investigate the oncogenic potential of HOX11, we targeted its expression in lymphocytes of transgenic mice by placing the human cellular DNA under the transcriptional control of Ig heavy chain or LCK regulatory sequences. Only IgHmu-HOX11 mice expressing low levels of HOX11 were viable. During their second year of life, all HOX11 transgenic mice became terminally ill with more than 75% developing large cell lymphomas in the spleen, which frequently disseminated to thymus, lymph nodes, and other nonhematopoietic tissues. Lymphoma cells were predominantly clonal IgM+IgD+ mature B cells. Repopulation of severe combined immunodeficient mice with cells from hyperplastic spleens indicated that the HOX11 tumor phenotype was transplantable. Before tumor development, expression of the transgene did not result in perturbations in lymphopoiesis; however, lymphoid hyperplasia involving the splenic marginal zones was present in 20% of spleens. Our studies provide direct evidence that expression of HOX11 in lymphocytes leads to malignant transformation. These mice are a useful model system to study mechanisms involved in transformation from B-lineage hyperplasia to malignant lymphoma and for testing novel approaches to therapy. They represent a novel animal model for non-Hodgkin's lymphoma of peripheral mature B cell origin.
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PMID:A model for spontaneous B-lineage lymphomas in IgHmu-HOX11 transgenic mice. 981 90

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