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Query: UMLS:C0079731 (B-cell lymphoma)
 16,671 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Aggressive B-cell lymphomas are occurring with increasing incidence among individuals infected with human immunodeficiency virus (HIV). Several lines of evidence implicate both Epstein-Barr virus (EBV) and c-myc activation in the pathogenesis of a major subset of these tumors. These observations prompted our investigation of interactions among EBV, c-myc, and HIV in primary B cells. We show that nonimmortalized peripheral B lymphocytes from EBV-seropositive, HIV-seronegative donors can be infected by HIV and that a subset of these lymphocytes become transformed. Malignant transformation was documented by several criteria. These cells displayed altered growth properties, propagating in 1% serum and cloning in soft agar, and formed invasive tumors of Burkitt lymphoma phenotype after subcutaneous injection into severe combined immunodeficiency mice. Such cells revealed marked enhancement of EBV DNA and RNA and of endogenous c-myc transcripts and protein. HIV-1 infection of already immortalized B-cell lines led to a similar upregulation of EBV and c-myc transcripts. These data indicate that HIV has properties of a transforming retrovirus, as it mediates two events linked to B-cell neoplasia: deregulation of c-myc and activation of EBV. They also raise the possibility of a role for HIV, apart from induction of immune suppression, in the pathogenesis of B-cell lymphoma in the acquired immune deficiency syndrome.
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PMID:Human immunodeficiency virus induction of malignant transformation in human B lymphocytes. 165 56

Patients with congenital and acquired immunodeficiencies are at increased risk for the development of B-cell lymphoproliferative disorders. When the appropriate tests have been performed, the Epstein-Barr virus (EBV) nuclear antigen (EBNA) or EBV DNA has been found in tissues from these tumors. These data have provided support for the idea that these tumors are associated with EBV. In this article we report about a child with severe combined immunodeficiency (SCID) who developed a malignant B-cell lymphoma that was not associated with EBV. The B-cell lymphoma in the patient proved to be, by hybridization analysis of immunoglobulin (Ig) heavy chain gene rearrangements of tumor-cell DNA, of clonal origin. However, neither EBNA nor EBV DNA could be detected in tumor tissue by anticomplement immunofluorescence or in situ cytohybridization with an EBV DNA probe. Furthermore, EBV DNA could not be detected by Southern blot hybridization using two EBV DNA hybridization probes on the same DNA blots that clearly contained the clonal Ig gene rearrangement. This case represents a clonal B-cell lymphoma occurring in a severely immunodeficient patient that was not associated with EBV. Antiviral chemoprophylaxis has been recommended for the prevention of EBV-related B-cell lymphoproliferations in transplant patients. Such prophylaxis may be ineffective in patients with B-cell lymphoproliferative disorders not associated with EBV.
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PMID:B-cell lymphoma in severe combined immunodeficiency not associated with the Epstein-Barr virus. 282 20

A 12-year-old boy with severe combined immunodeficiency who had been kept in a gnotobiotic environment since birth received bone marrow from a histoincompatible sibling in an attempt to reconstitute immunologic function. To prevent graft versus host disease, the donor's marrow was treated in vitro with monoclonal antibody and complement to remove alloreactive T cells. Eighty days after transplantation, the patient had a systemic illness characterized by fever, thrombocytopenia, gastrointestinal pain, and bleeding; he died on the 124th post-transplantation day. Postmortem examination revealed multiple tumor-like B-cell proliferations, recipient in origin, in numerous organs. Epstein-Barr virus (EBV) was isolated from the patient's pharyngeal secretions; EBV nuclear antigen was found in spontaneously transformed peripheral-blood lymphocytes, inflammatory cells from peritoneal fluid, and bone marrow cells; and EBV genomes were discovered in all tumor tissues. The donor's serum showed evidence of past EBV infection. Analysis of cellular immunoglobulin and immunoglobulin gene DNA from the tumors indicated both monoclonal and oligoclonal B-cell proliferations. These findings provide evidence for the evolution of EBV-induced polyclonal activation of B cells to oligoclonal B-cell proliferation and finally to monoclonal B-cell lymphoma.
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PMID:Epstein-Barr virus-associated B-cell proliferations of diverse clonal origins after bone marrow transplantation in a 12-year-old patient with severe combined immunodeficiency. 298 67

A 3 1/2-year-old girl with severe combined immunodeficiency received a thymus epithelial graft. After transient clinical and in vitro immunologic improvement, she developed fever, lung infiltrates and, terminally, massive gastrointestinal bleeding only 2 1/2 months after transplantation. Autopsy revealed widespread immunoblastic sarcoma involving both transplantation sites in the mesentery and thigh, lymph nodes, lung, liver, spleen and gastrointestinal tract. This B cell lymphoma was likely induced by the grafted thymus epithelium.
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PMID:Immunoblastic sarcoma after thymus epithelial graft in an immunodeficient child. 743 94

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

Bis-indolyl-(seco)-1,2,9a-tetrahydrocyclopropa[c]benz[e]indol-4-on e compounds are synthetic analogues of CC-1065 that are highly cytotoxic toward a broad spectrum of tumor cell lines. One of these compounds, called DC1, was conjugated to antibodies via novel cleavable disulfide linkers. Conjugates of DC1 with murine mAbs anti-B4 and N901 directed against tumor-associated antigens CD19 and CD56, respectively, proved to be extremely potent and antigen selective in killing target cells in culture. DC1 conjugates with humanized versions of anti-B4 and N901 antibodies were also constructed and demonstrated to be as cytotoxic and selective as the respective murine antibody conjugates. The anti-B4-DC1 conjugate showed antitumor efficacy in an aggressive metastatic human B-cell lymphoma survival model in SCID mice and completely cured animals hearing large tumors. Anti-B4-DC1 was considerably more effective in this tumor model than doxorubicin, cyclophosphamide, etoposide, or vincristine at their maximum tolerated doses.
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PMID:Enhancement of the selectivity and antitumor efficacy of a CC-1065 analogue through immunoconjugate formation. 754 85

Anti-CD19 monoclonal antibody anti-B4 (IgG1) conjugated to the novel toxin-blocked ricin forms a potent immunotoxin, anti-B4-blocked ricin, that kills greater than 4.5 logs of CD19-positive cells in vitro after a 24-h exposure to a conjugate concentration of 5 x 10(-9) M (1.11 micrograms/ml). The efficacy of anti-B4-blocked ricin in vivo was assessed in survival models of SCID mice bearing either a human B-cell lymphoma (Namalwa), a human non-T and non-B acute lymphoblastic leukemia (Nalm-6), or a murine B-cell lymphoma transfected with the human CD19 gene (300B4). In one model, 5 x 10(7) tumor cells were injected i.p., and 1 h later the mice were treated with i.v. bolus injections of anti-B4-blocked ricin at 100 micrograms/kg/day for 5 days. Controls included similar treatment with anti-B4 antibody (72 micrograms/kg/day or 2 mg/kg/day for 5 days) alone or with the isotype-matched nonspecific immunotoxin, N901-blocked ricin (100 micrograms/kg/day). In a second model, 4 x 10(6) tumor cells were injected i.v., and 7 days later mice were treated i.v. as above. Anti-B4-blocked ricin showed efficacy by killing in vivo up to 3 logs of tumor cells, which was manifested in significant prolongation of the life of the treated animals. Only very limited or no effects were observed in animals treated with either anti-B4 antibody alone or N901-blocked ricin control conjugate. The concentration of anti-B4-blocked ricin in the blood of animals was 150 ng/ml after the first i.v. injection and about 800 ng/ml following the fifth injection of conjugate. This increase may be due to damage to the reticuloendothelial system by anti-B4-blocked ricin, since the rate of clearance of carbon from blood also decreased 5-fold after five injections as compared to the rate after only one injection. These studies indicate that anti-B4-blocked ricin has the potential to increase survival times of hosts with malignant disease.
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PMID:Anti-B4-blocked ricin immunotoxin shows therapeutic efficacy in four different SCID mouse tumor models. 768 Feb 84

Despite advances in conventional therapy, many lives continue to be lost to common forms of B-cell cancers, including leukemias, lymphomas and multiple myeloma. We propose a novel approach to therapy of such cancers using controlled expression of a diphtheria toxin gene (DT-A) to kill malignant cells. We have previously demonstrated selective killing of various cell types, in vitro and in vivo, by cell-specific, transcriptionally controlled expression of this gene. Organ-specific ablation in otherwise healthy transgenic mice has convincingly demonstrated the exquisite specificity achievable by this technique. In the studies now described, DT-A was delivered in vitro and in vivo using a novel gene delivery system employing DNA physically attached to the exterior of adenovirus. After demonstrating the efficacy of gene delivery to Epstein-Barr virus transformed human B-cells in vitro, in vivo work was performed using a SCID mouse model for B-cell lymphoma, in which protection against tumor was observed. The concepts of tissue-regulated toxin gene therapy, and this novel adenovirus gene delivery system are discussed.
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PMID:Gene therapy for B-cell lymphoma in a SCID mouse model using an immunoglobulin-regulated diphtheria toxin gene delivered by a novel adenovirus-polylysine conjugate. 781 62

The t(14;18) translocation is found in the majority follicular lymphomas and some high grade B-cell lymphomas. This is results in deregulation of the BCL-2 gene and appears to play a role in oncogenesis. Various numbers of cells from a cell line derived spontaneously from a patient with B-cell lymphoma bearing the t(14;18) translocation and negative for the Epstein-Barr virus (EBV) were injected by IP, IV, and SC routes into SCID mice. The mice developed lymphoma bearing the t(14;18) translocation with as few as 5 x 10(6) cells within 28 days. This was determined by histological examination. The higher the cell inoculation the more rapidly the lymphoma developed. Engraftment of the tumour cells was determined by PCR for the t(14;18) breakpoint region on peripheral blood samples and could be detected prior to development of overt lymphoma. Having established a lymphoma model the cells were treated with antisense oligonucleotides to the first open reading frame of the BCL-2 gene prior to inoculation of the SCID mice. Control treatments with sense and nonsense oligonucleotides was also performed. At 28 days the sense, nonsense and untreated cell SCID mice had developed lymphoma, however, the antisense treated group failed to develop lymphoma. The findings demonstrate the modelling of B-cell lymphoma bearing the t(14;18) translocation and the ability to modify the lymphoma process with the use of antisense oligonucleotides to the BCL-2 gene. Reduction of the BCL2 protein suppresses the oncogenic potential of these lymphoma cells confirming that it plays an essential role in the development of malignancy.
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PMID:Antisense oligonucleotides suppress B-cell lymphoma growth in a SCID-hu mouse model. 808 13

At least 1% of organ transplant recipients develop Epstein-Barr virus-positive, often fatal lymphomas. EBV-positive cells accumulating in some organ transplant recipients were suggested to predict EBV+ lymphoma risk but no prospective study has been reported. We used the polymerase chain reaction (PCR) to detect EBV genomic sequences in successive blood samples of 60 kidney recipients before and up to 11 years after renal transplantation. Xenotransplantation of EBV-positive patient and -negative control samples into mice with severe combined immunodeficiency (SCID) was used to assess the tumor risk inherent in these samples. Despite single EBV+ cell detection sensitivity, none of the control samples was positive for EBV genomic sequences. In nearly 2/3 of patients EBV genomic DNA was detectable 3-6 months after transplantation for about 3 months. No patient developed lymphoma. Lymphocytes from 8 EBV-genome positive patients and 10 healthy donors were engrafted into 38 SCID mice. Human B cell lymphoma developed in 75% of the control grafts within about 3 months. In striking contrast, none of the patient grafts developed lymphoma despite the large numbers of EBV+ cells initially transplanted. Patient lymphocyte grafts were resistant to injection of live EBV, while in control lymphocyte grafts this caused lymphoma development within 3 weeks. We conclude that a 100-1000-fold expansion of circulating EBV+ B cell pools occurs frequently after organ transplantation and that it is balanced by effective EBV immunosurveillant functions resistant to immunosuppression. The mere detection of EBV genomic material was not predictive of lymphoma development.
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PMID:Epstein-Barr virus surveillance after renal transplantation. 817 44


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