Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0079731 (B-cell lymphoma)
 16,671 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Primary thymic B-cell lymphoma is clinically characterized by aleukemic, highly aggressive local growth, infrequent distant metastasis, and infrequent secondary lymph node involvement. VLA-1 to VLA-6 are cell surface molecules binding to matrix molecules such as collagen, fibronectin, epiligrin, and laminin. VLA-4 additionally binds to VCAM-1 and ICAM-2, thus mediating intercellular adhesion. Other molecules involved in cell/cell adhesion are LFA-1 (CD11a/CD18), Mac-1(CD11b/CD18) and their ligand ICAM-1 (CD54), p150,95 (CD11c/CD18), LFA-3 (CD58), CD44, and LECAM-1. Twenty-three tumors, together with normal lymphoid tissue, were immunohistochemically examined to investigate the expression pattern of these molecules in thymic B-cell lymphomas and in their putative normal counterparts, namely thymic medullary B cells. Thymic B-cell lymphomas consistently lacked VLA-1,-2,-3,-5,-6, and CD11b, expressed ICAM-1 in 21 of 23 cases but were heterogenous for VLA-4, LFA-1, CD11c, LFA-3, CD44, and LECAM-1. Presence of LFA-1 correlated with LFA-3 expression (P = 0.029). The receptor profile of thymic B-cell lymphoma was reminiscent of the expressional status of normal thymic medullary B cells in some aspects but deviated in others: Assuming that, in terms of differentiation, thymic B-cell lymphoma is related to the asteroid variant of thymic medullary B cells, a propensity to down-regulate/lose VLA-4, CD11a, CD44, and LECAM-1 would have to be supposed in conjunction with a tendency to overexpress ICAM-1 and LFA-3. Sclerosis as an inconsistent phenomenon in thymic B-cell lymphoma was absent in 8 of 23 tumors. Presence of sclerosis correlated with LECAM-1 expression of the tumor cells (P = 0.038). Recent studies suggest that a locally growing/aleukemic phenotype of a B-cell neoplasia might be determined by the phenotype VLAs-, LFA-1+, ICAM-1+, CD44-, and LECAM-1-. Our data corroborate this view.
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PMID:Adhesion receptor profile of thymic B-cell lymphoma. 138 63

Tumor growth is dependent in part on interactions between tumor cells and the extracellular matrix of host tissues. Expression of the cell surface glycoprotein CD44/Pgp-1, which mediates cell-substrate interactions is increased in many types of malignancies, but the role of CD44 in tumor growth is largely undefined. Recently, two isoforms of CD44 have been identified: an 80-90 kD form, which has high affinity for cell bound hyaluronate and a 150 kD form which does not mediate attachment to hyaluronate-coated surfaces. In this work, human B cell lymphoma cells stably transfected with cDNA clones encoding either of the two CD44 isoforms were compared for tumorigenicity and metastatic potential in nude mice. Expression of the 80-90 kD form but not the 150 kD form of CD44 greatly enhanced both local tumor formation and metastatic proclivity of the lymphoma cells. Our results suggest that CD44 polypeptides may play an important role in regulating primary and metastatic tumor development in vivo.
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PMID:Distinct effects of two CD44 isoforms on tumor growth in vivo. 191 39

Tumor dormancy can be induced in a murine B cell lymphoma (BCL1) by immunizing BALB/c mice with the tumor immunoglobulin (Ig) before tumor cell challenge. In this report, we have investigated the immunological and cellular mechanisms underlying the induction of dormancy. BCL1 tumor cells were injected into SCID mice passively immunized with antibody against different epitopes on IgM or IgD with or without idiotype (Id)-immune T lymphocytes. Results indicate that antibody to IgM is sufficient to induce a state of dormancy. Antibodies against other cell surface molecules including IgD and CD44 (Pgp1) had no effect on tumor growth. Id-immune T cells by themselves also had no effect on tumor growth in SCID mice. However, simultaneous transfer of anti-Id and Id-immune T cells enhanced both the induction and duration of the dormant state. In vitro studies indicated that antibody to IgM induced apoptosis within several hours and cell cycle arrest by 24 h. Hyper cross-linking increased apoptosis. The Fc gamma RII receptor played little or no role in the negative signaling. Antibodies that did not negatively signal in vitro did not induce dormancy in vivo. The results suggest that anti-IgM plays a decisive role in inducing tumor dormancy to BCL1 by acting as an agonist of IgM-mediated signal transduction pathways.
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PMID:Tumor dormancy and cell signaling. II. Antibody as an agonist in inducing dormancy of a B cell lymphoma in SCID mice. 753 41

CD44 is a major cell-surface receptor for hyaluronate (HA). By alternative RNA-splicing a large number of CD44 variants are generated. To explore the role of CD44 splicing in the regulation of cell binding to HA, three different isoforms of CD44 were transfected in the CD44 negative B-cell lymphoma line Namalwa and in the fibroblastoid cell line COS7. We observed that whereas the standard form of CD44 (CD44s) mediated adhesion of Namalwa to HA, Namalwa transfected with CD44v3-10 or CD44v8-10 was unable to bind to either immobilized or soluble HA. After stimulation of CD44 with an activating anti-CD44 mAb or with phorbol ester, the binding of CD44s to HA was 5- to 10-fold higher than that of the other two isoforms. By contrast, COS7 cells transfected with CD44s, CD44v8-v10, or CD44v3-v10 bound equally effectively to HA. Hence, in addition to alternative splicing, cell type determines CD44 binding to HA.
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PMID:Binding of cell-surface expressed CD44 to hyaluronate is dependent on splicing and cell type. 754 90

Diffuse large B-cell lymphoma in the Revised European-American Lymphoma Classification encompasses various morphologic subtypes of diffuse large-cell lymphomas of B-cell origin. The category is biologically and clinically heterogeneous, even though it constitutes approximately 30% of all non-Hodgkin's lymphomas. Clinically, the International Prognostic Index that identifies high-risk group in aggressive non-Hodgkin's lymphomas is widely accepted. Lacking, however, are biologic or molecular prognostic markers that might aid in understanding the pathogenesis and designing specific therapies. CD44 isoforms are involved in tumor dissemination and might be associated with aggressive behavior of non-Hodgkin's lymphomas. We studied immunohistochemical expression of CD44s and CD44v6 in the tumors and examined their clinical significance in a cohort of patients with primary nodal diffuse large B-cell lymphoma who were uniformly evaluated and treated with doxorubicin-containing chemotherapy (n = 42). In contrast to CD44s signals, CD44v6 signals were weak in routinely processed non-Hodgkin's lymphoma sections. Therefore, we used a highly sensitive catalyzed reporter deposition system and successfully detected CD44v6 signals in diffuse large B-cell lymphomas. Overexpression of the isoform was verified by Southern blot of reverse transcription polymerase chain reaction products. CD44s and CD44v6 were positive in 17 (40%) of 42 and 13 (31%) of 42, respectively. CD44v6 was detected predominantly in lymphoma cells, whereas CD44s was often positive for nonneoplastic small lymphocytes as well. In univariate regression analysis, the B symptoms, being in the International Prognostic Index high-risk group, and CD44v6 expression emerged as significant parameters for poorer overall survival, but CD44s expression did not achieve statistical significance. When multivariate regression analysis was performed using the former three parameters, only CD44v6 expression remained significant (P = .017; relative risk = 3.48), indicating that CD44v6 is a molecule particularly important for predicting worse prognosis. CD44v6, which can be detected in the archival materials, might be a biologically and clinically useful marker in identifying the high-risk group in the diffuse large B-cell lymphoma category of the Revised European-American Lymphoma Classification.
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PMID:Prognostic significance of CD44v6 in diffuse large B-cell lymphoma. 1034 95

The Revised European-American Lymphoma classification gives Burkitt-like lymphoma (BLL) provisional status, leaving unresolved the differential diagnosis with Burkitt lymphoma (BL) and diffuse large B-cell lymphoma (DLBCL). This study compared the biologic features of adult BLL and DLBCL. The phenotypic distinction between BLL and DLBCL was determined by immunohistochemical staining of frozen tissue from 13 patients with BLL and 55 patients with DLBCL by using an extensive antibody panel including Ki-67, CD10, CD11a/lymphocyte function-associated antigen 1alpha (LFA-1alpha), CD18/LFA-1beta, CD58/LFA-3, and CD54/intercellular adhesion molecule, CD8 for tumor-infiltrating cytotoxic T cells (T-TILs), CD44 homing receptor, and p53 and Bcl-2 oncogenic proteins. Compared with DLBCL, BLL had a higher proliferative rate (mean Ki-67, 88% versus 53%), greater expression of CD10 and p53 antigens, and decreased expression of Bcl-2. BLL cases had a consistent absence of one or more cell adhesion molecules (92% versus 27%), low T-TIL numbers, and absence of CD44 homing receptor (92% versus 14%). The t(8;14) translocation was identified in 80% of BLL cases, but no patients with BLL had the t(14;18) translocation. In a 10-year analysis, median survival of patients with BLL was 1.2 years, and that of patients with DLBCL was 2.5 years. Although the proportion of patients cured was similar in the 2 groups, BLL patients had an increased risk of early death. We conclude that BLL can be recognized by its combined morphologic and phenotypic features and that it represents a high-grade lymphoma much closer to BL than DLBCL. Retention of the BLL category or inclusion of BLL as a variant of BL is biologically and clinically more appropriate than absorbing the category of BLL into DLBCL. (Blood. 2001;97:3713-3720)
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PMID:The Burkitt-like lymphomas: a Southwest Oncology Group study delineating phenotypic, genotypic, and clinical features. 1138 7

Activation-induced cytidine deaminase (AID) induces somatic hypermutation (SHM), class switch recombination (CSR), and immunoglobulin gene conversion in B-lymphocytes. Here we report for the first time the expression of AID in healthy human B-lymphocytes and in B-cell non-Hodgkin lymphomas (B-NHL). AID mRNA expression in humans is restricted to the CD19(+)CD38(+)IgD(-) germinal center cells, namely the CD19(+)CD38(+)CD44(-) centroblasts. After in vitro stimulation of naive human B cells by CD40-L and IL-4, AID mRNA is strongly induced for only 48 hours. In a survey of human B-NHL AID was found to be constitutively expressed in follicular lymphoma and in diffuse large B-cell lymphoma but to be absent in B-precursor lymphoblastic leukemia, in mantle cell lymphoma, and in plasma cell myeloma. In B-cell chronic lymphatic leukemia, in immunocytoma, and in extranodal marginal zone B-cell lymphoma of MALT, AID mRNA was expressed only in some samples. In follicular lymphoma and diffuse large B-cell lymphoma, the expression of AID mRNA was coincident with the presence of SHM in the variable region exons of the immunoglobulin heavy-chain gene. In human B-NHL, the AID mRNA is spliced into 4 different variants but does not contain point mutations. Thus AID, which is highly regulated during healthy B-cell development, is constitutively expressed in human germinal center B-NHL and in subsets of nongerminal center B-NHL. This constitutive expression of AID may promote illegitimate DNA recombinations and somatic mutations in B-NHL.
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PMID:Expression of activation-induced cytidine deaminase in human B-cell non-Hodgkin lymphomas. 1251 17

The lymphoid follicle is a specialized microenvironment for the differentiation of antigen (Ag)-activated B cells; the major stromal cell components in lymphoid follicle are the follicular dendritic cells (FDCs). At the same time, most of the B-cell lymphomas originate from the germinal center, and the generation and blast transformation of B-cell lymphoma occurs in close association with FDCs in the early stage of tumorigenesis. To study the functional roles of FDCs in lymphomagenesis, we established an inducible tumor model. The human B-cell lymphoma cell line, L3055, formed solid tumors only when inoculated with an FDC line, HK. In addition, 2 FDC-signaling molecules (FDC-SMs), a novel protein 8D6 and 4G10/CD44, are required for tumor formation in vivo, because monoclonal antibodies (mAbs) specific to these 2 proteins inhibited lymphomagenesis completely when they were inoculated with L3055 and HK cells. However, these 2 FDC-SMs have distinct functional roles in tumor formation. FDC-SM-8D6 enhances L3055 cell proliferation, whereas FDC-SM-4G10/CD44 inhibits its apoptosis. Identification of the functional roles of these critical FDC-SMs may lead to the discovery of therapeutic drugs that suppress the survival and growth of lymphoma cells.
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PMID:Novel follicular dendritic cell molecule, 8D6, collaborates with CD44 in supporting lymphomagenesis by a Burkitt lymphoma cell line, L3055. 1509 Apr 45

The demonstration that Abs to adhesion molecules can block tumor metastasis suggested their use for therapy. However, such Abs affect nonmalignant cells as well. To circumvent this adverse effect, we proposed the use of bispecific Abs that bind simultaneously to an adhesion receptor and to a tumor-specific Ag. Such bifunctional Abs bind more avidly to tumor cells that coexpress both target Ags than to normal cells. The Id of the surface Ig of malignant B lymphocytes is a tumor-specific Ag. Therefore, we produced bispecific Abs with specificity to the adhesion molecule, CD44, and to an idiotypic determinant of the murine B cell lymphoma, 38C-13. These anti-Id x anti-CD44 bispecific Abs blocked 38C-13 cell adhesion to hyaluronic acid, while not affecting adhesion of Id-negative cells. In vivo studies demonstrated that the bispecific Abs inhibited lymphoma cell dissemination to the lymph nodes, bone marrow, and spleen, and prolonged survival of tumor-bearing mice. Migration of 38C-13 cells to the lymphoid organs was inhibited by the bispecific Abs. Thus, the bispecific Ab-mediated reduction in metastasis resulted, at least in part, from reduced homing to these organs. In contrast to anti-CD44 monospecific Abs, the anti-Id x anti-CD44 bispecific Abs did not affect immune responses such as delayed-type hypersensitivity. Hence, bispecific Abs against adhesion molecules and tumor-specific Ags may selectively block tumor metastasis in a way which may leave at least part of the immune system intact.
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PMID:Anti-idiotype x anti-CD44 bispecific antibodies inhibit invasion of lymphoid organs by B cell lymphoma. 1538 11

Morphologic features of Burkitt lymphoma (BL) and diffuse large B-cell lymphoma (DLBCL) overlap. No single phenotypic marker or molecular abnormality is pathognomonic. We tested a panel of 8 germinal center (GC) and activated B-cell (ABC) markers for their ability to separate BL and DLBCL. We diagnosed 16 BL and 39 DLBCL cases from 21 patients with AIDS and 34 without AIDS based on traditional morphologic criteria, Ki-67 proliferative index, and c-myc rearrangement (fluorescence in situ hybridization). After immunohistochemically staining tissue microarrays of BL and DLBCL for markers of GC (bcl-6, CD10, cyclin H) and ABC (MUM1, CD138, PAK1, CD44, bcl-2), we scored each case for the percentage of positive cells. Hierarchical clustering yielded 2 major clusters significantly associated with morphologic diagnosis (P < .001). For comparison, we plotted the sum of the GC scores and ABC scores for each case as x and y data points. This revealed a high-GC/low-ABC group and a low-GC/high-ABC group that were associated significantly with morphologic diagnosis (P < .001). Protein expression of multiple GC and ABC markers can separate BL and DLBCL.
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PMID:Germinal center and activated b-cell profiles separate Burkitt lymphoma and diffuse large B-cell lymphoma in AIDS and non-AIDS cases. 1620 84


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