Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:Q06643 (non-Hodgkin's lymphoma)
 11,307 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The establishment of Clusters of Differentiation for T- and B-lymphoid cells during International Workshops on Human Leukocyte Differentiation Antigens prompted the authors to evaluate the immunophenotypes in 160 cases of non-Hodgkin's lymphoma (NHL). In this group, 130 were of B-lymphocyte lineage (117 by monotypic immunoglobulin expression), and 30 of T-cell lineage. In the B-NHL series the expression of immunoglobulin isotypes, B-cell maturation/differentiation antigens of CD9, CD10, CD19-24, CD37, and CD38 (OKT10), HLA-DR and peanut agglutinin binding showed no significant relationship with histopathologic diagnosis as defined by the Kiel classification. Of the T-cell markers, CD5, CD6, and CD7 showed lineage promiscuity by their presence on some B-NHL. Conversely, the authors grouped the cases according to phenotypes (either CD antigens or immunoglobulin isotypes) which occur in distinct stages of (physiologic) B-cell maturation/differentiation. Eighty-six of the 130 cases could be fitted according to CD phenotype expression. This approach did not yield a significant relationship between phenotype and individual histopathologic categories either. The staging by CD phenotype and by immunoglobulin isotype yielded different results in this respect. Most B-NHL had an intermediate stage of B-cell maturation/differentiation. In the T-NHL series most cases showed a phenotype (CD1-CD8, CD38, TdT, and peanut agglutinin binding capacity) compatible with mature T-lymphocyte characteristics. The exceptions were lymphoblastic convoluted lymphomas, which exhibited an immature immunophenotype. It is concluded that NHL in distinct histopathologic categories are heterogeneous in immunologic phenotypes, and that the immunophenotype of lymphoma cells has no evident association with that of their presumed counterparts in physiologic cell maturation/differentiation.
 ...
PMID:Immunophenotyping of non-Hodgkin's lymphoma. Lack of correlation between immunophenotype and cell morphology. 331 Jun 50

To develop an effective tumor immunotherapy for B-lineage non-Hodgkin's lymphoma (NHL) and acute lymphoblastic leukemia (ALL), a bispecific monoclonal antibody (BsAb) has been generated with the first specificity for the CD3 epsilon-chain and the second for the CD19 antigen. Peripheral blood mononuclear cells (PBMCs) isolated from patients with NHL or ALL during remission or relapse rapidly proliferated (up to 179-fold increase) on in vitro activation combining phytohemagglutinin or CD3 monoclonal antibody with interleukin-2. After 3 weeks of stimulation, more than 90% of the PBMCs was CD3+ and CD8+, even when cultures were started with only 5% CD3+ cells. Cytotoxic activity against autologous malignant B cells was markedly enhanced (from 5% baseline to 70% lysis) by the addition of the CD3 x CD19 BsAb in all samples tested. Immunophenotypic examination of a series of tumor target cells showed that all samples examined showed CD54 (intercellular adhesion molecule-1) and HLA class I, but showed no B7 expression. CD11a (lymphocyte function-associated antigen-1) expression was heterogeneous. Various types of experiments showed that efficient CD3 x CD19 BsAb-mediated cytolytic capacity was not dependent on expression of either of these surface proteins. This contrasts with normal major histocompatibility complex-restricted antigen-specific cytotoxicity and may be essential for effective in vivo application of this BsAb.
 ...
PMID:Killing of autologous B-lineage malignancy using CD3 x CD19 bispecific monoclonal antibody in end stage leukemia and lymphoma. 751 19

Although initially thought to be a B lineage restricted antigen, low "density" or antibody binding capacity (ABC) CD20 has recently been detected on subset(s) of normal T lymphocytes (Hultin et al.: Cytometry 14:196-204, 1993). We report low ABC CD20 expression in three (two children, one adult) cases of T-acute lymphoblastic leukemia (T-ALL). CD20 and other pertinent antigens were detected using a direct dual color method with a Becton Dickinson FACScan flow cytometer and Simulset software. Only one cell population based on light scatter was noted in each case that immunophenotypically represented almost a pure population of malignant cells expressing T lymphocyte antigens (for example, CD7 98%, 92%, and 100%, respectively). A total of 95%, 87%, and 79% of the cells from the three cases expressed CD20 with an unusual low ABC compared to the customary "bright" CD20 expression on normal B lymphocytes. Other B lymphocyte associated antigens, such as CD19, CD22, Dr, and immunoglobulin light chains, were negative. Eleven other T lymphocytic malignancies from 1991 to 1993 were CD20 negative, including three other case of T-ALL (one adult and two children). One unusual case of intestinal small lymphocytic non-Hodgkin's lymphoma with a natural killer/T lymphocytic immunophenotype not described in this report appeared to be CD20"dim"+. Low ABC CD20 expression by T lymphocytic malignancies may provide a more unique immunophenotypic "fingerprint" to help support the diagnosis of T cell neoplasia vs. normal/reactive T cells (for example, low ABC CD20 cells represent only 2.4 +/- 1.5% of normal peripheral blood lymphocytes). This characteristic might also facilitate monitoring patients for residual or recurrent disease.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Low level CD20 expression on T cell malignancies. 752 45

Seven patients with low-grade non-Hodgkin's lymphoma were treated with a combination of a murine monoclonal antibody directed against the B-cell-specific antigen CD19 (CLB-CD19), given twice weekly, and continuous infusion of low-dose recombinant interleukin-2 (rIL-2). We demonstrated stable serum CLB-CD19 levels throughout the 12 weeks of treatment, and homing of the antibody into the tumour sites. A variable degree of antigenic modulation was noted. Prolonged treatment resulted in a sustained increase in the number of natural killer cells in the circulation with enhanced cytotoxic capacity, including antibody-dependent cellular cytotoxicity. During the first weeks of treatment, T cell activation occurred in the majority of patients. Toxicity was related to the rIL-2 treatment and consisted of transient constitutional symptoms and a flu-like syndrome without organ dysfunction. A partial remission occurred in one patient, and in another patient who was primarily leukaemic a greater than 50% reduction of circulating B cells was noted. An antitumour effect occurred early during treatment and could not be related to rIL-2-induced modulation of natural killer cell or T lymphocyte activation.
 ...
PMID:Treatment of low-grade non-Hodgkin's lymphoma with continuous infusion of low-dose recombinant interleukin-2 in combination with the B-cell-specific monoclonal antibody CLB-CD19. 753 Jan 70

The origin of the Reed-Sternberg cell, the neoplastic cell of Hodgkin's disease, has not been defined. We evaluated a case of Hodgkin's disease, mixed cellularity type, which presented in the retroperitoneum of a 45-year-old woman. Reed-Sternberg cells and Hodgkin's cells expressed the characteristic markers CD15 and CD30. In addition, they expressed the B-cell antigens CD19 and CD20, as well as CD45/leukocyte common antigen. Clonal rearrangement of the immunoglobulin heavy chain gene was detected by Southern blot analysis. These results suggest that some cases of Hodgkin's disease are derived from an activated cell of lymphoid origin. This case documents a close relationship between Hodgkin's disease and non-Hodgkin's lymphoma, and it demonstrates that even when newer ancillary techniques are employed these two entities can have overlapping features.
 ...
PMID:Hodgkin's disease, mixed cellularity type, with a B-cell immunophenotype. Report of a case and literature review. 753 89

To evaluate the potency by which human T cells are targeted and activated by bispecific monoclonal antibodies (BsAbs) to lyse tumor cells, a clonogenic assay was developed. The efficacy of a CD3 x CD19 BsAb binding to both the CD3 T-cell antigen and the CD19 B-cell antigen was already proven in 51Cr-release assays and in 3-day activation cultures. To achieve more quantitative results, a 14-day clonogenic assay, based on limiting-dilution, was performed for the determination of the initial and residual number of clonogenic units obtained with a CD19+ pre-pre-B acute lymphoblastic leukemia (ALL-B) cell line. Elimination of up to 5 logs of ALL-B cells by freshly isolated peripheral blood mononuclear cells (PBMCs) cultured with BsAb plus interleukin-2 (IL-2) could be detected. The presence of human IgG did not abolish the effect. Repeated addition of each of the two agents was necessary, because a single treatment produced only a 1- to 2-log kill. CD3 monoclonal antibody and IL-2 stimulation ("lymphokine-activated killer cell" conditions) resulted in only a 2-log kill. The number of T cells proved critical in lysis of ALL-B cells, with a 5-log kill using a T-cell:B-cell ratio of 3:1 but with only a 1-log kill using a ratio of 1:1. PBMCs isolated from patients with non-Hodgkin's lymphoma, both in relapse or remission, proved to be as competent as those from healthy donors in removing ALL-B cells. This clonogenic assay shows the importance of repeated administration of CD3 x CD19 BsAb and IL-2 and offers the possibility to compare it with other therapies in B-cell malignancy.
 ...
PMID:The efficacy of CD3 x CD19 bispecific monoclonal antibody (BsAb) in a clonogenic assay: the effect of repeated addition of BsAb and interleukin-2. 753 21

Diffuse large B cell lymphomas (DLBLs) represent a heterogeneous collection of aggressive non-Hodgkin's lymphomas that can arise either de novo or as a result of transformation from chronic lymphocytic leukemia, small lymphocytic lymphoma, follicular lymphomas, or lymphomas of mucosa-associated lymphoid tissue. A small percentage of DLBLs express the CD5 antigen. The majority of these cases have evolved from a pre-existing low grade non-Hodgkin's lymphoma (Richter's syndrome). However, we identified and characterized nine CD5-positive DLBLs in which the patients did not have a previous history or concomitant evidence of chronic lymphocytic leukemia, small lymphocytic lymphoma, follicular lymphoma, or mucosa-associated lymphoid tissue-associated non-Hodgkin's lymphoma, suggesting that they arose de novo. All nine cases expressed CD20 and monotypic immunoglobulin, all eight cases examined expressed CD19, CD22 and CD43, eight of the nine cases expressed HLA-DR, and two of eight cases expressed CD11c. None of the cases expressed CD3, CD10, CD11b, CD21, CD23 or CD30. CD5 expression by these cells was found to be identical to that of CD5-positive B cell chronic lymphocytic leukemia by quantitative polymerase chain reaction analysis of CD5 mRNA. These nine de novo CD5-positive DLBLs exhibited clonal immunoglobulin heavy and light chain gene rearrangements but lacked integration of the Epstein-Barr virus genome and structural alterations of the bcl-1, bcl-2, c-myc, H-ras, K-ras, and N-ras proto-oncogenes and the p53 tumor suppressor gene. However, bcl-6 proto-oncogene rearrangement, which is involved in chromosome band 3q27 aberrations, was found in four cases (44.4%). This is comparable with the frequency of bcl-6 gene rearrangement in CD5-negative DLBL. In contrast, bcl-6 gene rearrangement was absent in six cases of DLBL associated with Richter's syndrome. These findings suggest that de novo CD5-positive DLBLs are genotypically similar to CD5-negative DLBLs and may be pathogenetically distinct from the DLBLs associated with Richter's syndrome.
 ...
PMID:De novo CD5-positive and Richter's syndrome-associated diffuse large B cell lymphomas are genotypically distinct. 754 11

Idarubicin (Ida), an analogue of daunomycin, was linked to a mouse monoclonal antibody against the B cell differentiation antigen CD19. Determination of the activity of both the antibody and drug moieties was carried out in vitro using a pre-B cell human acute lymphoblastic leukaemia cell line (NALM-6). A 23% loss in antibody binding and a 20-fold loss in drug activity were observed upon conjugation. Selective cytotoxicity for CD19+ cells, however, was obtained. Measurement of the cytotoxicity, antibody activity and release of the breakdown product, 14-OH-Ida, showed that the conjugates remained stable for more than 100 days after lyophilization and storage at -20 degrees C. In vivo studies were performed in irradiated nu/nu mice bearing NALM-6 tumours. Initial dose response studies with free idarubicin demonstrated that three i.p. doses (every other day) of 10 micrograms resulted in little antitumour activity, but the death of all the animals by day 23. The same treatment regime using 15 micrograms Ida-anti-CD19 conjugate caused the disappearance of four out of five tumours with three complete cures and no evidence of toxicity as assessed by weight loss. Administration of a conjugate of idarubicin with an irrelevant antibody at this dose led to no significant antitumour response. The administration of free drug at a dose of 6 micrograms resulted in a minor antitumour response but high toxicity, whereas injection of Ida-anti-CD19 conjugate at this dose caused no toxicity and a substantial antitumour effect with eradication of two out of five tumours. These results clearly demonstrate that the administration of Ida-anti-CD19 conjugates can result in complete tumour regression in an experimental model. Idarubicin-containing immunoconjugates should be useful for the treatment of patients with non-Hodgkin's lymphoma.
 ...
PMID:Preclinical investigation of the antitumour effects of anti-CD19-idarubicin immunoconjugates. 768 21

The cell line described here was established for a 50-year-old male patient with rapidly progressive non-Hodgkin's lymphoma whose marrow was diffusely infiltrated with large granular lymphocytes (LGL). Immunophenotyping of marrow blasts and peripheral lymphocytes was positive for CD56, CD2 and CD7, and negative for CD3. Cytotoxicity of peripheral blood mononuclear cells at an effector: target (E:T) cell ratio of 50:1 was 79% against K562 cells and 48% against Daudi cells. To establish the line, cells from the peripheral blood were placed into enriched alpha medium containing 12.5% fetal calf serum, 12.5% horse serum, 10(-4) M beta-mercaptoethanol and 10(-6) M hydrocortisone. Growth of the line (termed NK-92) is dependent on the presence of recombinant IL-2 and a dose as low as 10 U/ml is sufficient to maintain proliferation. Conversely, cells die within 72 h when deprived of IL-2; IL-7 and IL-12 do not maintain long-term growth, although IL-7 induces short-term proliferation measured by 3H-thymidine incorporation. None of the other cytokines tested (IL-1 alpha, IL-6, TNF-alpha, IFN-alpha, IFN-gamma) supported growth of NK-92 cells which have the following characteristics: surface marker positive for CD2, CD7, CD11a, CD28, CD45, CD54, CD56bright; surface marker negative for CD1, CD3, CD4, CD5, CD8, CD10, CD14, CD16, CD19, CD20, CD23, CD34, HLA-DR. DNA analysis showed germline configuration for T-cell receptor beta and gamma genes. CD25 (p55 IL-2 receptor) is expressed on about 50% of all cells when tested at 100 U/ml of IL-2 and its expression correlates inversely with the IL-2 concentration. The p75 IL-2 receptor is expressed on about half of the cells at low density irrespective of the IL-2 concentration. NK-92 cells kill both K562 and Daudi cells very effectively in a 4 h51-chromium release assay (84 and 86% respectively, at an E:T cell ratio of 5:1). The cell line described here thus displays characteristics of activated NK-cells and could be a valuable tool to study their biology.
 ...
PMID:Characterization of a human cell line (NK-92) with phenotypical and functional characteristics of activated natural killer cells. 815 60

High-grade B-cell-type non-Hodgkin's lymphomas are observed in 5% to 8% of patients positive for the human immunodeficiency virus. Nearly all cases belong to one of the three major histologic types: centroblastic or large noncleaved cell, immunoblastic and Burkitt's lymphoma, or small noncleaved cell. Some cases that are polymorphic are termed high-grade B-cell, not otherwise specified (NOS). The authors determined the immunophenotype of each histologic category of acquired immunodeficiency syndrome (AIDS)-related non-Hodgkins' lymphoma and sought a relationship with the presence of the Epstein-Barr virus (EBV). B-cell differentiation antigens, activation marker expression (human leukocyte antigen-DR, CD10, CD19, CD20, CD21, CD22, CD23, CD25, CD30, CD38), and epithelial membrane antigen were analyzed. The clonality was determined by the detection of cytoplasmic immunoglobulin, surface immunoglobulin, and the analysis of joining region (JH) immunoglobulin gene configuration by Southern blot. Epstein-Barr virus was detected either by Southern blot analysis using BamHI W probe fragment or by in situ hybridization with EBV-encoded RNA transcripts-1 specific probe. The immunophenotypic and genotypic results were compared with the morphology results and with the presence or absence of EBV. Burkitt's lymphomas were associated with EBV in 50% of cases, were monoclonal, and expressed mostly immunoglobulin (Ig) MK, CD10, CD19, CD20, CD22, and CD38. This immunophenotypic profile closely resembled those of the centroblastic cases (large noncleaved cell), in which EBV was absent. Epstein-Barr virus was associated with 90% of immunoblastic cases, and only CD10, CD20, and CD38 were expressed. CD71 was expressed in all categories of non-Hodgkin's lymphoma, and CD21 and CD23 were rarely expressed. Two cases of immunoblastic lymphoma and one case of high-grade B-NOS were polyclonal regarding JH rearrangement, but EBV tested with 1.9-Kb Xhol fragment was clonal. No significant immunophenotypic changes were noted in relation to the presence of EBV. Such studies comparing morphology, immunophenotype, and genotype could help classify and better understand the pathogenesis of AIDS-related non-Hodgkin's lymphoma.
 ...
PMID:Immunophenotypic and genotypic analysis of acquired immunodeficiency syndrome-related non-Hodgkin's lymphomas. Correlation with histologic features in 36 cases. French Study Group of Pathology for HIV-Associated Tumors. 820 68


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>