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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)

Little is known about the role of tumor infiltrating T lymphocytes (TIL-T) in the pathogenesis of malignant diseases and collaboration between normal and malignant cells has not yet been proved. In the present work, we have investigated whether immune T lymphocytes exist in tumors invaded by B-cell non-Hodgkin's lymphoma (NHL) or Hodgkin's disease (HD). Therefore, we have studied the reactivity of the CD45RA monoclonal antibody, which discriminates between naive and memory CD4 T lymphocytes. Our results showed far lower percentages of CD4+ CD45RA+ in malignant lymphoma (30.3 +/- 15.0% in B-cell NHL, and 37.4 +/- 18.6% in HD) than in reactive hyperplasia (54.7 +/- 13.2%), leading to the conclusion of an accumulation of immune cells in tumor microenvironment. A further heterogeneity in the relative proportion of naive and memory TIL-T was also observed within lymphoma (range: 11 to 68% in B-cell NHL, 5 to 69% in HD). In B-cell NHL, it was related to histological features, as documented by the Kiel classification (P = .028), and to a stronger extent to cytological characteristics analysed with the Grenoble classification (P less than .0001): class 1 NHL, which are essentially indolent NHL displayed lower naive cells (22.2 +/- 7.4%) than class 3 NHL, which are more aggressive (40.1 +/- 16.1%). Among the monoclonal antibodies (mAb) defining the B-cell clone phenotype or activation state (CD19, CD20, CD21, CD22, CD23, CD24, CD5, CD10, CD11a, and Ki67), only CD23 (P = .0003) and Ki67 (P = .0007) revealed statistical association with the percentage of naive CD4 lymphocytes. No correlation could be demonstrated with the proportion of whole TIL-T, activated CD3 DR TIL-T, or CD4 subset.
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PMID:CD45RA expression by CD4 T lymphocytes in tumors invaded by B-cell non-Hodgkin's lymphoma (NHL) or Hodgkin's disease (HD). 153 69

Detailed immunophenotypic analyses of immunologically classified leukemias and lymphomas showed that CD40 displays an exquisite B-lineage specificity within the human lymphopoietic system. Notably, 82% of B-lineage chronic lymphocytic leukemias (CLLs), 82% of B-lineage hairy cell leukemias (HCLs), 86% of B-lineage non-Hodgkin's lymphomas (NHLs), and 29% of B-lineage acute lymphoblastic leukemias (ALLs) were CD40+. Quantitative analyses of the correlated expression of CD40 and other B-lineage differentiation antigens on fetal lymphoid precursor cells by multiparameter two-color/three-color flow cytometry, combined with analyses of sequential antigen expression on fluorescence-activated cell fluorescence activated cell sorter (FACS) isolated immunologically distinct fetal B-cell precursor subpopulations during in vitro proliferation and differentiation, provided evidence that the acquisition of CD40 antigen in human B-cell ontogeny occurs subsequent to the expression of CD10 and CD19 antigens but before the surface expression of CD20, CD21, CD22, CD24, and surface immunoglobulin M (sIgM). Some leukemic pro-B cells from ALL patients as well as normal pro-B cell clones from fetal livers displaying germline Ig heavy chain genes were CD40+, indicating that the acquisition of CD40 antigen likely precedes the rearrangement of Ig heavy chain genes. CD40+ FACS-sorted malignant cells from B-lineage ALL as well as B-lineage NHL patients were capable of in vitro clonogenic growth, indicating the CD40 antigen is expressed on clonogenic leukemia and lymphoma cells. This hypothesis was confirmed by the ability of an anti-CD40 immunotoxin that we used as an antigen-specific cytotoxic probe to effectively kill clonogenic B-lineage ALL and NHL cells.
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PMID:Temporal association of CD40 antigen expression with discrete stages of human B-cell ontogeny and the efficacy of anti-CD40 immunotoxins against clonogenic B-lineage acute lymphoblastic leukemia as well as B-lineage non-Hodgkin's lymphoma cells. 170 26

From 1983 to 1989 we performed a prospective trial of 70 consecutive, in vitro purged autologous bone marrow transplants (BMT) for patients with progressive non-Hodgkin's lymphoma. Forty-nine patients had responsive disease at the time of transplantation while 21 others had refractory high risk lymphoma. Forty-two patients with B-lineage lymphoma received autologous marrow purged in vitro with monoclonal antibody (anti CD9, CD10, CD24) plus complement, 12 with T-lineage lymphoma received monoclonal antibody immunotoxins (anti CD5, CD7-ricin conjugates) along with 4-hydroperoxycyclophosphamide purging and 16 received unpurged marrow. All received cyclophosphamide, 57 with fractionated total body irradiation, and 13 with BCNU and cytarabine. Hematologic engraftment was prompt and unaffected by phenotype (B vs. T) or by in vitro purging used (B vs. T vs. none) although nine of 16 non-relapse deaths were related to poor graft function. Fifty-one patients (73%) were alive in complete remission (CR) 1 month following transplantation while 15 patients (12 with initially refractory disease) had persistent disease. Subsequently, 41 +/- 18% (by Kaplan-Meier estimate; +/- 95% confidence limits) of those who achieved CR remained relapse free 1-6.4 (median 3) years post-BMT. Neither risk group, purging, nor immunophenotype predicted subsequent post-transplant relapse. Among those 51 who achieved CR, 13 of 43 (27 +/- 14%) with responsive disease survive disease free while three of eight (38 +/- 34%) refractory patients survive disease free (p = 0.96). Overall, 24 patients survive, 16 in continuous complete remission 1-6.5 years following transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Autologous bone marrow transplantation for progressive non-Hodgkin's lymphoma: clinical impact of immunophenotype and in vitro purging. 193 55

Two atypical human non-Hodgkin's lymphomas (NHLs) that exhibited unusual genotypic and in situ immunophenotypic abnormalities are described. Immunophenotypically, both NHLs lacked surface Ig heavy chains. With the exception of the MB2 B-cell-associated antigen, no B- and T-cell differentiation antigen was detected in case 1. NHL 2 failed to show evidence of clonality by immunohistochemical analysis but revealed the presence of many B-lymphocytes with an abnormal phenotypic profile: CD19+, CD20+, CD22+, kappa-, lambda-, CD9-, CD10-, CD21-, and CD24-. Genotypic analysis indicated that both lymphomas derived from anomalously matured pre-B-cells that had rearranged the lambda or kappa light chain genes but not the Ig heavy chain gene. The neoplastic cells of the two NHLs resemble the light chain-only B-cells recently discovered, following Epstein-Barr virus immortalization, in the human bone marrow. The authors' data confirm, therefore, the existence of the light chain-only B-cells in the human hematopoietic compartment. Moreover, their results emphasize the conclusive role of the immunogenotypic analysis in defining clonality, lineage, and maturation abnormalities of such atypical NHLs.
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PMID:Genotypic and immunophenotypic characterization of two human light chain-only B-cell non-Hodgkin's lymphomas. 212 Oct 20

A new B-cell line (ONHL-1) was established from non-Hodgkin's lymphoma. ONHL-1 was free from Epstein-Barr virus nuclear antigen and expressed CD20, CD24, and slg (mu, delta, gamma and kappa), thus being equivalent to the mature B-cell stage. Chromosome analysis revealed a markedly abnormal pattern including 14q+ and 6q-. In accordance with the positive expression of surface kappa light chains, one of the kappa genes was found to be rearranged. However, rearrangement of the lambda locus was also detected, contrary to the supposed hierarchy for the rearrangement of the light-chain genes. Further, the rearranged fragments of the JH, C lambda, and bcl-2 genes were of the same size in the EcoRI and HindIII digests on the same filter. This may suggest that the bcl-2 gene is juxtaposed with the JH and C lambda locus. The proliferation of ONHL-I was inhibited by adding Staphylococcus aureus Cowan 1 or 12-O-tetradecanoyl-phorbol-13-acetate. During this growth inhibition, the expression of c-myc decreased, while that of bcl-2 mRNA remained steady. This result suggests that not the bcl-2 gene but other oncogenes, such as c-myc, play a key role in the proliferation of ONHL-1. This agrees with the hypothesis that the bcl-2 gene is not concerned with aggressive proliferation but with cell survival. This new cell line will therefore be of value in studying the differentiation and tumorigenesis of B cells.
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PMID:Establishment and characterization of a new human B-cell line (ONHL-1) from non-Hodgkin's lymphoma: constant expression of bcl-2 gene during mitogen-induced growth inhibition. 224 98

This study investigates the applicability of immunocytochemical techniques towards improving the cytological diagnosis of lymph node disorders. Cytocentrifuge preparations of fine needle aspirates were examined using an indirect immunoperoxidase method and the alkaline phosphatase-antialkaline phosphatase method. 36 reactive lymph nodes were evaluated. 23 patients showed T cell predominance as assessed by the presence of CD3+ cells. 13 patients showed an excess of CD24+ cells over CD3+ cells. In all patients the B cell population showed no light chain class restriction. 48 aspirates from patients with B-non-Hodgkin's lymphoma of low malignancy were investigated. The majority of the cells in each of these cases expressed CD24 and 47 cases were monoclonal with respect to their light chain determinants. In 37/48 cases the antibody OKT9 reacted with less than 15% of cells. 18 aspirates were obtained from patients with B-non-Hodgkin's lymphoma of high malignancy. 17 patients showed light chain class restriction and a high percentage of CD24+ (greater than 80%) and OKT9+ (greater than 40%) cells. 8 malignancies were considered to be of T-cell origin. A low percentage (less than 15%) of Ig+CD24+ cells with a high number of CD3+ and/or CD4+ cells suggests a T-cell lymphoma. The majority of neoplastic cells in peripheral T-cell lymphomas (excluding mycosis fungoides) expressed OKT9 and CD3 expression was found to be variable. In 15 cases of Hodgkin's disease, there were 11 correct cytologic diagnoses. A significant number of BerH2 (CD30)+ cells having the morphology of Sternberg-Reed cells supports this diagnosis. 25 aspirates were obtained from patients with metastatic malignant tumours. Marker studies in eight cases helped in distinguishing metastatic malignant tumours from malignant lymphomas. Our findings indicate that the immunocytochemical technique is applicable to cytological material and that the simplicity of the procedure merits application to routine diagnostic cytology.
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PMID:The value of immunocytochemical staining of lymph node aspirates in diagnostic cytology. 306 42

In a retrospective analysis the authors studied the relation between the immunologic phenotype of B-cell non-Hodgkin's lymphoma (NHL) and disease-free survival. The phenotype included immunoglobulin isotypes; B-cell maturation/differentiation antigens of clusters of differentiation CD9, CD10, CD19-24, CD37, CD38; T-lymphocyte antigens in CD5-7; HLA-DR; peanut agglutinin binding capacity; terminal deoxynucleotidyl transferase; the activation marker CD25 (interleukin-2 receptor); and the proliferation marker transferrin receptor. The phenotype and clinical data were available for 109 patients. Two patients underwent bone marrow transplantation, and 15 patients (with low or intermediate grade NHL) did not receive treatment intended to achieve complete remission. These 17 cases were excluded from the analysis. For individual markers, CD23 expression was associated with a longer actuarial disease-free survival (50% survival in CD23-positive cases was 40 months; and in CD23-negative cases, 16 months; P = 0.01). Among the total study population of 92 patients, this finding applied in particular to those with a low-grade malignancy according to the Kiel classification (P = 0.03). In high-grade NHL (Kiel classification) the absence of CD38 or presence of CD24 on tumor cells correlated with a higher degree of disease-free survival (P values 0.009 and 0.04, respectively). For a combination of five CD markers associated with stages in physiologic B-lymphocyte maturation/differentiation (CD9, CD10, CD21-23), the lowest measure of disease-free survival was observed where NHLs were at an immature stage, and the greatest extent of survival where NHLs were associated with a resting B-cell stage (P = 0.006). These statistical significances aside, the detailed immunologic phenotyping has relatively little prognostic value when compared with that of the malignancy grade assessed by conventional histopathology.
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PMID:Immunophenotyping of non-Hodgkin's lymphoma. Correlation with relapse-free survival. 325 75

The severe combined immunodeficient (SCID) mouse model is an important tool with which to study new strategies for treating hematologic neoplasia. For these experiments, a large number of human cell lines growing in SCID mice are a prerequisite. We describe a new Epstein-Barr virus (EBV)-positive B cell line, designated BEVA, with a complex karyotype including translocations t(14:18)(q32;q21) and t(4;11) (q21;q23) that meets this need. As demonstrated by Southern blot analysis, BCL2 at 18q21, but not MLL/ALL1 at 11q23, was involved in these translocations. BEVA cells coexpressed lymphoid (IgG-kappa, CD19, CD20, CD21, and CD24) and myeloid (CD11b, CD15, and CDw65) markers. Interestingly, the cell line was established from the bone marrow culture of a patient with acute myeloid leukemia (AML). Examination of bone marrow biopsy specimens suggested the presence of non-Hodgkin's lymphoma (NHL) in this patient in addition to AML. In vitro and in vivo growth characteristics of the BEVA cell line were compared with the previously described EBV-positive B cell line DoHH2, also carrying a translocation t(14;18)(q32;q21). These DoHH2 cells additionally expressed CD10, whereas, in contrast to BEVA cells, only a small population of DoHH2 cells showed expression of CD44. Both cell lines showed similar growth characteristics in vitro, but reacted differently to cytokines, including interleukin (IL)-4, IL-6, IL-7, and alpha-interferon (IFN). Upon inoculation in SCID mice, marked differences were observed in the dissemination patterns of the BEVA or DoHH2 cells. Although both cell lines circulated in the blood and were predominantly found in murine bone marrow and lymphoid tissues, DoHH2 cells infiltrated the murine spleens, whereas BEVA cells could only rarely be detected in these tissues. In contrast to DoHH2 cells, BEVA cells gave rise to tumor masses in liver, kidney, and para-aortal or mesenteric lymph nodes. The relationship between these in vitro differences and the observed differences in dissemination of both cell lines is discussed.
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PMID:Characterization of a novel malignant B cell line with t(14;18) and t(4;11) established from a patient with acute monoblastic leukemia. 929 3

In our study we used for definition of leukemia/lymphoma cells a new parameter which allows the enumeration of mean fluorescence intensity expressed by the number of antigen molecules per cell. Quantitative immunofluorescence using calibration microbeads was performed in 36 patients with different acute and chronic lymphoid and myeloid leukemia and in 19 healthy volunteers. We showed that quantitative immunophenotyping allowed the definition of aberrant marker densities on neoplastic cells. We demonstrated under- and overexpression of CD8 marker in CD3/CD4/CD8 complex in T acute lymphatic leukemia and T non-Hodgkin's lymphoma and T leukemia of large granular lymphocytes as compared to normal counterparts. We pointed out that certain antigens (e. g. CD10, CD4, CD24) were expressed at different levels on different cell subsets (CD10 in early B-acute lymphatic leukemia and coexpressed in T-acute lymphatic leukemia, CD4 on T cells and monocytes, CD24 on B cells and granulocytes in chronic myeloid leukemia). We showed that quantitative immune fluorescence could provide new data contributing to a more precise definition of cell differentiation. We documented the significant difference between antigen density of early and late markers in B-cell and myeloid malignancies. Further, we demonstrated that quantitative immune phenotyping could help in determination of exact definition of pathologic clone in morphologically immature leukemia population and showed that parameters of this method are also convenient for cytoplasmic marker evaluation. In our study we were able to demonstrate that CD45 quantitative expression appeared to be a more informative parameter than its percentage of antigen-positive cells as a measure of antigen expression only and we pointed out that low and high CD45 densities enabled to differentiate between pathological clone and residual healthy population in examined sample. We showed that quantitative immune phenotyping could be another important parameter for definition of leukemia phenotype suitable for detection of minimal residual disease.
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PMID:Quantitative immunocytofluorometry--new parameters for the definition of leukemia cells. 960 6

Immunodeficiency-related B-cell disorders are seen after organ transplantation and in congenital and acquired immunodeficiency states. Post-transplant lymphoproliferative disorders (PTLD) comprise a histologic spectrum ranging from hyper-plastic appearing lesions to frank non-Hodgkin's lymphoma or multiple myeloma histology. Multiple clones may co-exist, representing a uniquely different mechanism for lymphomagenesis. The incidence varies from 1% in renal recipients to 8% in lung recipients, but can be markedly increased by the use of anti-T-cell therapies, or by T-cell depletion in bone marrow transplantation. Pre-transplant EBV seronegativity increases risk to as high as 30%-50%. More than 90% of tumors are EBV-associated. Mechanisms for viral lymphomagenesis remain incompletely defined; LMP-1 may function as an oncogene and coprecipitates with TRAF, BCL-2 overexpression has also been identified. A possible direct tumorigenic effect has recently been suggested for cyclosporine. PTLD has a highly variable clinical picture, certain patterns are however seen. Reversibility of PTLD with reduction in immunosuppressives has long been recognized. Predicting reversibility has been difficult. The presence or absence of BCL-6 mutations has recently been identified as being of predictive value. Surgical resection can be curative. Cytotoxics, although problematic, can also be curative. Long term remission has been achieved with anti CD21 and CD24 antibodies; efficacy has been reported anecdotally for interferon alpha and for rituximab. In vitro expanded EBV-specific T cells have been effective as treatment and as prophylaxis in the setting of bone marrow transplantation. EBV viral load measured in blood appears to correlate with the emergence of PTLD and may facilitate prophylactic studies. PTLD is a model of immunodeficiency related EBV lymphomagenesis. Pathogenetic, therapeutic, and prophylactic insights gained from the study of PTLD are likely to be applicable to other immunodeficiency states and to EBV-related lymphoid neoplasia in general.
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PMID:Diagnosis and treatment of transplant-related lymphoma. 1070 78


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