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)

To analyze the transition of an autoimmune disease into a mucosa-associated lymphoid tissue-non-Hodgkin's lymphoma (MALT-NHL), we investigated a total of 27 cases of clinically diagnosed autoimmune thyroiditis with lymphoid hyperplasia. Three cases of thyroid hyperplasia served as controls. Monoclonal B cells were detected by studying rearrangement patterns of the hypervariable CDR III regions within the immunoglobulin heavy chain gene locus and the T-cell receptor gamma chain gene (TCRG). We used a seminested polymerase chain reaction (PCR) to demonstrate immunoglobulin rearrangements and a multiplex PCR for TCRG rearrangements. The PCR products were analyzed by temperature gradient gel electrophoresis to expand mixtures of homo- and hetero-duplices within heterogeneous populations of B cells. With this approach we found monoclonality in 14 of the 27 cases of Hashimoto's disease. In a reinvestigation we discovered additional histological and immunohistochemical features of MALT-NHL in 17 cases. The 14 cases of thyroiditis with clonally expanded B cells clearly demonstrate the transition from autoimmune disease to non-Hodgkin's lymphoma.
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PMID:Temperature gradient gel electrophoresis for analysis of clonal evolution in non-Hodgkin's lymphoma of the thyroid. 758 52

PBPC harvesting was performed in two patients with advanced-stage low-grade non-Hodgkin's lymphoma after mobilization with dexa-BEAM chemotherapy plus G-CSF. The collected grafts were subjected to immunomagnetic purging using B cell-specific moAbs and paramagnetic beads. Immunophenotypic and/or molecular analysis of the resulting products (PCR amplification of t(14;18) or CDR-III rearrangements) demonstrated successful depletion of lymphoma cells. Rapid and durable hematopoietic recovery occurred after reinfusion of the purged grafts following myeloablative radiochemotherapy (9-10 days to neutrophils > 0.5 x 10(9)/l; 9-11 days to platelets > 20 x 10(9)/l). We conclude that effective immunomagnetic purging of PBPC grafts is feasible without affecting engraftment.
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PMID:Rapid engraftment of peripheral blood progenitor cell grafts purged with B cell-specific monoclonal antibodies and immunomagnetic beads. 852 84

In B-cell non-Hodgkin's lymphoma (NHL), as in other B-cell malignancies, clonal rearrangement of the third complementarity determining region (CDR III) of the immunoglobulin heavy chain gene (IgH) provides a useful marker for the detection of minimal residual disease (MRD) after treatment. To determine the clinical utility of IgH polymerase chain reaction (PCR), we analyzed peripheral blood (PB) and bone marrow (BM) samples from 25 patients with NHL with no PCR detectable chromosomal rearrangement who have undergone autologous bone marrow transplantation (ABMT). Patients with histologic bone marrow infiltration at the time of bone marrow harvest were selected for study since this provided us with diagnostic tissue samples. As an initial strategy DNA was amplified using consensus variable (VH) and joining (JH) region primers. In those cases failing to amplify using consensus region primers, PCR was performed using a panel of VH family-specific framework region 1 (FR1) primers. The clonal products were directly sequenced. From the V-N-D region nucleotide sequences, clone specific probes were constructed and used for subsequent detection of MRD. A clonal PCR product could be PCR amplified and directly sequenced in 18 (72%, 90% confidence intervals 54%-86%) of these 25 patients, 8 with diffuse and 10 with follicular NHL. Eight of these 18 patients have relapsed after ABMT. All had detectable lymphoma cells before relapse and the sequence of the CDR III region at the time of relapse was identical to that obtained at the time of ABMT. All 10 patients who remain in complete remission from 18 to 36 months after ABMT had eradication of PCR detectable lymphoma cells after ABMT, although in three patients PCR detectable MRD was detected early after ABMT. We conclude that sequencing and the use of patient specific IgH CDR III oligonucleotides probes provides a simple and highly reliable method to determine the specificity of the IgH PCR technique. The clinical utility of this technique is demonstrated by the finding that eradication of PCR detectable lymphoma cells in these patients is associated with decreased relapse after ABMT (P = .0002).
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PMID:Eradication of polymerase chain reaction detectable immunoglobulin gene rearrangement in non-Hodgkin's lymphoma is associated with decreased relapse after autologous bone marrow transplantation. 889 95

Five patients with non-Hodgkin's lymphoma (NHL) and 4 patients with chronic lymphocytic leukaemia (CLL) were treated with the CDR-grafted (rat x human) monoclonal antibody (mAb) Campath-1H (anti-CD52). Tumour regression was noted preferentially in peripheral blood and in the bone marrow but lymph nodes were less affected. Normal blood B and T cells were profoundly reduced in all patients whereas CD16+ NK cells and CD14+ monocytes decreased marginally. In all responding CLL patients CD52-negative T but not B cells appeared during treatment and persisted for several months (4-19+) during unmaintained follow-up. Clonal T cells defined as a predominance of a single T cell receptor (TCR) V gene usage, in one case verified by TCR CDR3 fragment analysis and nucleotide sequencing, emerged within the CD52-/CD8+ cell population during Campath-1H therapy in 2 CLL patients, both achieving a long-lasting remission. The increase in CD8+ T cell expansions (up to 23-fold) during unmaintained remission and follow-up suggest that the clonal CD8+ cells may represent regulatory T cells controlling the growth of the tumour B cell clone. Clonal T cells might thus be a target for an immune therapeutic intervention in B cell tumours.
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PMID:Clonal CD8+ and CD52- T cells are induced in responding B cell lymphoma patients treated with Campath-1H (anti-CD52). 902 Mar 67

LL2 is an anti-CD22 pan-B-cell monoclonal antibody which, when radiolabeled, has a high sensitivity for detecting B-cell, non-Hodgkin's lymphoma (NHL), as well as an antitumor efficacy in therapeutic applications. The aim of this study was to determine whether intracellularly retained radiolabels have an advantage in the diagnosis and therapy of lymphoma with LL2. In vitro studies showed that iodinated LL2 is intracellularly catabolized, with a rapid release of the radioiodine from the cell. In contrast, residualizing radiolabels, such as radioactive metals, are retained intracellularly for substantially longer. In vivo studies were performed using LL2-labeled with radioiodine by a non-residualizing (chloramine-T) or a residualizing method (dilactitol-tyramine, DLT), or with a radioactive metal (111In). The biodistribution of a mixture of 125I (non-residualizing chloramine-T compared to residualizing DLT), 111In-labeled LL2 murine IgG2a or its fragments [F(ab')2, Fab'], as well as its humanized, CDR-grafted form, was studied in nude mice bearing the RL human B-cell NHL cell line. Radiation doses were calculated from the biodistribution data according to the Medical International Radiation Dose scheme to assess the potential advantage for therapeutic applications. At all assay times, tumor uptake was higher with the residualizing labels (i.e., 111In and DLT-125I) than with the non-residualizing iodine label. For example, tumor/blood ratios of 111In-labeled IgG were 3.2-, 3.5- and 2.8-fold higher than for non-residualizing iodinated IgG on days 3, 7 and 14, respectively. Similar results were obtained for DLT-labeled IgG and fragments with residualized radiolabels. Tumor/organ ratios also were higher with residualizing labels. No significant differences in tumor, blood and organ uptake were observed between murine and humanized LL2. The conventionally iodinated anti-CD20 antibody, 1F5, had tumor uptake values comparable to those of iodinated LL2, the uptake of both antibodies being strongly dependent on tumor size. These data suggest that, with internalizing antibodies such as LL2, labeling with intracellularly retained isotopes has an advantage over released ones, which justifies further clinical trials with residualizing 111In-labeled LL2 for diagnosis, and residualizing 131I and 90Y labels for therapy.
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PMID:Advantage of residualizing radiolabels for an internalizing antibody against the B-cell lymphoma antigen, CD22. 919 78

Three established Burkitt's lymphoma (BL) cell lines (Daudi, Raji and DG-75) and three B-non-Hodgkin's lymphoma (B-NHL) of other types (Pfeiffer, Farage and Toledo) were analyzed with respect to the presence of somatic point mutations in their rearranged immunoglobulin Vkappa genes. Two of the Vkappa sequences of BL and two of those of the B-NHL were heavily mutated (up to 11%), when compared with their closest germline variable region counterparts ("clonal mutations"). Only one of the six cell lines contained an unmutated germline Vkappa sequence. The clonal mutations have features characteristic of the mutation machinery operating in the course of the T-dependent immune response, such as a preference of mutations in purine bases, more transitions than transversions and targeting to CDR and to known "hotspot" motifs. Sequence variations among different Vkappa PCR clones isolated from each of the cell lines ("intraclonal mutations") showed that the Vkappa of Toledo exhibited about 5-fold higher mutation frequency (MF) than the background level of Taq polymerase error (approximately 0.12% mut/bp). Similarly, the MF of Vkappa of two of the BL cell lines was 3-4-fold higher than the Taq polymerase misincorporation rate. In contrast, the mutation frequencies of the Vkappa of DG-75, Farage and Pfeiffer did not significantly exceed the level of Taq polymerase error. Our combined results show that 5 out of the 6 B-cell lines studied originated from B-cells that have already somatically mutated in vivo their rearranged Vkappa genes. Moreover, two of the Burkitt's and one of the B-NHL cell lines exhibit intraclonal variation indicating that the process of somatic hypermutation continued following the neoplastic event, either in vivo or in culture. These results are in accord with the presumed origin of the majority of the BL and some types of the B-NHL, from centrocytes or centroblasts of the germinal centers in which the process of somatic hypermutation is taking place.
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PMID:Somatic mutations and intraclonal variations in the rearranged Vkappa genes of B-non-Hodgkin's lymphoma cell lines. 1048 73

A 32 year old female smoker (20 pack years) presented with an asymptomatic lymphocytosis of 13,000/nl and splenomegaly. The patient's blood smear showed an absolute lymphocytosis with 65% atypical lymphocytes. A total of 1% of the lymphocytes were bilobulated. Bone marrow histology and immunphenotyping of blood and bone marrow excluded leukemia and non-Hodgkin's lymphoma. IgH-CDR-3 PCR analysis revealed a polyclonal pattern. In summary, a persistent polyclonal B-cell-lymphocytosis (PPBL) was diagnosed. The exact etiology of PPBL is still unclear, however, it is associated with a polyclonal raise in the lymphocyte count of CD27+IgD+-memory-B-lymphocytes due to a defect in apoptosis signaling and leukocyte homing to secondary lymphoid tissues. An association with cigarette smoking is obvious since all patients are smokers. From all published cases, only two developed a malignancy with an uncertain association with PPBL. We have been monitoring our patient for 6.5 years without any evidence of the development of a lymphoma.
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PMID:[Asymptomatic 32 year old female smoker with persistent polyclonal lymphocytosis]. 1728 65