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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)

We reasoned that the SCID-hu mouse could provide an appropriate lymphoid or stromal microenvironment to support the growth of primary human lymphoma. Heterotransplantation of nine cases of primary T-cell non-Hodgkin's lymphoma (NHL) into untreated SCID mice and SCID mice reconstituted with human fetal thymus, spleen, and liver (SCID-hu) resulted in the development of lymphoid tumors in five (56%) cases. Two clonal T-cell NHL grew after a mean of 90 days after injection of primary lymphoma cell suspensions into the thymus xenografts in SCID-hu mice and failed to grow in a variety of sites in SCID mice, except for small tumors that developed after a long (157-day) latency period after intracranial injection of tumor cell suspensions into weanling SCID mice. Successful serial transplantation of NHL in SCID and SCID-hu mice required the presence of a human lymphoid or tumor microenvironment, and was enhanced by pretreating the SCID mice with 175 rad radiation and antiasialo antisera. Analysis of the primary and transplanted T-cell tumors showed identical patterns of T-cell surface markers by flow cytometry and immunophenotyping of fixed tissue sections, and, in one case, reactivity with a specific monoclonal antibody to V beta 5.1. Genotyping of the transplanted tumors showed T-cell receptor gene rearrangements identical to those present in the primary tumors. In one case, the presence of Epstein-Barr virus-positive B cells in association with the primary tumor resulted in the growth of a lymphoblastoid B-cell neoplasm in addition to the malignant T-cell lymphoma after transplantation of tumor fragments to SCID mice. The data support the hypothesis that a human lymphoid microenvironment enhances the growth of T-cell NHL in SCID mice. The SCID-hu thymus graft provides an apparently unique microenvironment that supports the growth of primary T-cell NHL, and can be used to study the interaction between lymphoma cells, nontransformed lymphoid cells, and the surrounding stromal microenvironment in vivo.
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PMID:Growth of primary T-cell non-Hodgkin's lymphomata in SCID-hu mice: requirement for a human lymphoid microenvironment. 182 59

Individuals with either primary or secondary immunodeficiencies are at high risk to develop not only infections but also malignancy (especially of the lymphoid system). The major focus of this paper is on malignancies that develop in immunodeficiency syndromes, particularly malignancies in naturally occurring immunodeficiencies and following bone marrow transplantation (BMT). As of August, 1986, 514 cases of naturally occurring immunodeficiencies have been registered at the Immunodeficiency Cancer Registry. Overall non-Hodgkin's lymphomas predominate in these patients, accounting for 48.6% of all cases. Non-Hodgkin's lymphoma is the predominant malignancy in ataxia-telangiectasia, common variable immunodeficiency, Wiskott-Aldrich syndrome (WAS) and severe combined immunodeficiency (SCID). The histopathology of the lymphomas differs somewhat in each of the disorders. In WAS, large cell "histiocytic" lymphoma predominates, with most cases having the features of B lymphocytes, including pleomorphic immunocytoma and immunoblastic lymphoma. Non-Hodgkin's lymphoma in SCID also generally has B cell features and in some cases multiple copies of Epstein-Barr virus (EBV) genomic DNA have been found in tumor tissue. In contrast to ataxia-telangiectasia, in which non-Hodgkin's lymphoma is also the predominant neoplasm, the morphology and cell marker characteristics are more similar to those seen in nonimmunodeficient children. The lymphomas in ataxia-telangiectasia are very heterogeneous with representation from all the major histologic subtypes. We have found no relationship between the degree of immunodeficiency and the development of malignancy. Immunodeficiency following BMT, as in naturally occurring immunodeficiencies, appears to predispose patients to the development of lymphoid malignancy, especially for recipients of partially mismatched bone marrow. In Minnesota 8 patients have developed B cell lympho-proliferative disorders (BLPD) following BMT.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Relationship of immunodeficiency to lymphoid malignancy. 284 Jun 29

Primary lymphoma of the central nervous system (CNS), including reticulum cell sarcoma, microglioma, and histiocytic lymphoma, represents less than 1% of all primary brain tumors. In the last 10 years, this tumor has tripled in frequency in the nonimmunosuppressed population. By 1991, the tumor will be the most common neurological neoplasm by virtue of the increase in sporadic occurrence and in the acquired immunodeficiency syndrome (AIDS) population. Three percent of AIDS patients will develop this tumor either prior to AIDS diagnosis or during their subsequent course. In addition to acquired immunosuppression, patients with inherited disorders (such as Wiskott-Aldrich syndrome, severe combined immunodeficiency, and X-linked immunodeficiency) and other acquired disorders of the immune system are predisposed to the development of CNS lymphoma. Immunological studies have suggested a role for Epstein-Barr virus in the production of this tumor. Although subtypes exist, non-Hodgkin's lymphoma of the CNS most commonly consists of histiocytic cells or large immunoblastic cells bearing B cell surface markers in close proximity to the lateral and third ventricles. Sixty percent of these deposits are multiple, and subarachnoid invasion is seen in one-quarter of patients. Vitreous involvement of the eye occurring prior to and during the course of CNS lymphoma has been noted in up to 25% of patients. The involvement of multiple areas of the neuraxis, the eye, and multiple intracranial sites often occurs in the absence of obvious systemic lymphoma. Therapeutic trials of brain radiation therapy are associated with median survivals of less than 1 year. Uniform complete responses of intracranial deposits are recorded following chemotherapy with high-dose intravenous methotrexate, CHOP (cyclophosphamide, hydroxydaunomycin/doxorubicin, Oncovin (vincristine), and prednisone), high-dose cytosine arabinoside, and intra-arterial methotrexate with barrier modification.
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PMID:Primary central nervous system lymphoma. 328 32

Local tumor growth has been reported after subcutaneous and intraperitoneal injection of Hodgkin's disease (HD) derived cell lines into different immunodeficient mouse strains. An animal model with disseminated growth of tumor cells would be useful for studying the in vivo biology of HD cells as well as for preclinical testing of new therapeutic regimens. For this purpose the HD-derived cell lines L540, L540cy, L428, and KM-H2 were injected intravenously into SCID mice. In contrast to L428 and KM-H2, widespread neoplasia occurred after a period of four to six weeks following injection of L540 and the subline L540cy. Lymph nodes were found to be the preferred site of tumor growth. CD30 surface antigen expression on Hodgkin cells and the karyotype of the tumor cells were preserved in the animal host. Thus, to a large extent, the SCID mouse model mimics the dissemination pattern of Hodgkin's disease in man. To evaluate the role of adhesion molecule expression in the dissemination of HD-derived cell lines, CD44 and members of the immunoglobulin, integrin, selectin, and Fc receptor families were quantified by flow cytometry. CD30 expression was also measured. Although CD44 expression has been correlated with dissemination in non-Hodgkin's lymphoma (NHL), this was not the case in the Hodgkin's SCID mouse model. CD44 was not expressed on the disseminating cell lines L540 and L540cy but was expressed in the nondisseminating lines L428 and KM-H2.
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PMID:Disseminated growth of Hodgkin's-derived cell lines L540 and L540cy in immune-deficient SCID mice. 751 37

B cell non-Hodgkin's lymphoma (B-NHL) occurring in immunocompromised hosts, such as acquired immune deficiency syndrome (AIDS) patients, is a high-grade malignancy resistant to regular chemotherapy. To determine whether immunotherapy with public anti-Ig idiotype antibodies can be used to treat these NHL, the Ig idiotype specificity of six NHL in AIDS patients (AIDS-ML) and 23 B-NHL experimentally induced in immunocompromised mice (SCID mice) was investigated. One of the six AIDS-ML and two of the 23 experimental B-NHL reacted monoclonally with a single public antibody, while one AIDS-ML and three experimental B-NHL reacted polyclonally with two or three different antibodies. The presence of Ig idiotypic polyclonality requires special consideration with regard to the introduction of anti-Ig idiotype immunotherapy in these cases.
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PMID:Immunoglobulin idiotypic specificity of AIDS-associated lymphomas and their experimental model. 764 34

Epstein-Barr virus (EBV) is a causative agent of malignant lymphomas occurring in immunocompromised hosts. Similar lymphoid tumors can be induced in mice with severe combined immunodeficiency (SCID mice) by transplanting human B-cells with latently infected EBV. We have previously observed that when apparently EBV-negative lymphomas were engrafted into SCID mice, 11 of 18 T-cell non-Hodgkin's lymphomas (NHLs) produced EBV associated lymphomas, but only 2 of 30 engrafted with B-NHLs. Previous studies suggested that EBV-infected cell inducing lymphomas in SCID mice may preferentially exist in T-cell NHL tissues. To prove this assumption, in situ hybridization (ISH) using oligonucleotide probes for EBV-encoded small RNAs 1 (EBER1) was used in this study to demonstrate EBV-bearing lymphocytes in NHL tissues. It was found that EBV-bearing cells existe in 9 of the 10 T-cell NHL surgical specimens. By contrast, in B cell NHLs, only 2 of 10 carried EBV-bearing cells. Further semi-quantitative analysis demonstrated that apparently significantly more EBV-bearing cells were present in T-cell NHL tissues than in B-cell NHLs. Moreover, these EBV-bearing cells in lymphoma tissues were shown to be of B-cell lineage, by the combinated analysis of immunostaining with CD20 and ISH with EBER1. These results indicated the increase of EBV-bearing B-cells in T-cell NHL tissues, suggesting the activation of B-cells with latently infected EBV by neoplastic T-cells.
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PMID:Increased number of Epstein-Barr virus latently infected B-cells in T-cell non-Hodgkin's lymphoma tissues. 766 94

Recurrent abnormalities of the short arm of chromosome 9, including translocations and interstitial deletions, have been reported in both leukemia and lymphoma. The pathologic consequences of these abnormalities remain unknown. The cyclin-dependent kinase 4 inhibitor (CDKN2) gene, which maps to 9p21, has been implicated by the finding of a high frequency of biallelic deletions in leukemic cell lines. We have determined the incidence of structural abnormalities affecting CDKN2 by DNA blot in a panel of 231 cases of leukemia and lymphoma and 66 cell lines derived from patients with lymphoid malignancies with defined cytogenetic abnormalities. Structural alterations of CDKN2 were seen in 20 (8.3%) of all fresh cases and 10 (15.1%) of all cell lines. Biallelic CDKN2 deletions were seen in 11 of 53 (21%) cases of B-cell precursor acute lymphoblastic leukemia (BCP-ALL). There was no association with any particular cytogenetic abnormality. Biallelic deletions were also found in high-grade and transformed non-Hodgkin's lymphoma (NHL) of both B- and T-cell lineages. In two cases of transformed NHL, analysis of sequential samples showed loss of CDKN2 with transformation. Neither deletions nor rearrangements of the CDKN2 gene were seen in any of the 119 leukemias of mature B or T cells analyzed. Biallelic deletions of CDKN2 were observed in 6 of 13 NHL cell lines. Three of the 6 cases had undergone transformation from low- to high-grade disease: in 2 of these cases it was possible to show that the CDKN2 deletions were present in fresh material from the patient and were therefore not an artifact of in vitro culture. Rearrangements of CDKN2 were seen in 2 cases (4%) of BCP-ALL, in 1 case of B-NHL, and in 1 Burkitt's lymphoma cell line and suggest the presence of a "hot spot" for recombination in the vicinity of the CDKN2 gene. These data indicate that the loss of CDKN2 expression may be involved in the pathogenesis of a subset of BCP-ALL, some high-grade NHL, and in the transformation of NHL from low- to high-grade disease. CDKN2 deletions and rearrangements occurred in the absence of detectable cytogenetic changes of chromosome 9p in 25 of 30 (83%) cases. Finally, of 10 cases of BCP-ALL that produced overt, transplantable leukemia in mice with severe combined immunodeficiency (SCID), seven showed biallelic CDKN2 deletions. In contrast, none of 11 cases that failed to engraft showed biallelic CDKN2 deletions. BCP-ALL cases that lack CDKN2 expression may have a particular propensity to grow in SCID mice.
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PMID:Deletions and rearrangement of CDKN2 in lymphoid malignancy. 784 11

Groups of SCID mice were injected with different PBMC sub-populations, and established LCL cells. In about 80% of PBMC-injected animals, tumors developed in association with high levels of human Ig in mouse serum and detectable IL-6 levels. The tumors showed a histopathologic pattern reminiscent of large cell immunoblastic non-Hodgkin's lymphoma; in situ hybridization invariably evidenced EBV sequences in a minority of cells. Genotypic analysis of tumors arising in PBMC-injected mice showed the presence of different oligoclonal B cell populations in different tumor sites. Southern blot analysis disclosed the presence of both linear (replicating) and episomal (latent) EBV DNA forms; sequential analysis of LCL cells serially passaged into animals revealed the progressive selection of clonal cells with only the latent episomal form. Attempts to dissect the events underlying tumor development revealed that the presence of T cells within the injected population was essential for tumor generation; however, the putative T cell-derived factors involved are unclear, and IL-6 seems to play a minor role.
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PMID:Properties of tumors arising in SCID mice injected with PBMC from EBV-positive donors. 815 96

To establish an in vivo model for the study of Hodgkin's disease and Reed-Sternberg (RS) cells, 25 lymph node tissue samples involved by Hodgkin's disease were grafted into severe combined immunodeficiency (SCID) mice. Ten Epstein-Barr virus (EBV)-associated tumors were obtained in SCID mice. EBV-positive tumors growing in SCID mice were correlated with the presence of EBV-positive nonneoplastic B cells in patient tumors (90% v 26.6%; P<.01) and was independent of the EBV status of RS cells. Our results suggested that EBV-positive tumors growing in SCID mice originated from normal EBV-positive small lymphocytes (bystander B lymphocytes). We also compared the characteristics of these tumors with those obtained after transplantation of 15 non-Hodgkin's lymphoma and four reactive lymph nodes. The latent period to observe a growing tumor in SCID mice was similar between the two groups (12.86 +/- 5.59 weeks for Hodgkin's disease v 13.6 +/- 5.36 weeks for non-Hodgkin's lymphoma and reactive lymph nodes). The relatively high number of EBV-positive small lymphocytes detected in Hodgkin's disease and T-cell lymphoma compared with B-cell lymphoma may account for the greater percentage of EBV-positive tumors obtained in SCID mice. Our results show that SCID mice do not provide the growth conditions that are required for in vivo growth of RS cells. We noted in some SCID tumors, the presence of binucleated and/or multinucleated giant cells resembling RS cells. However, the presence of such cells was not restricted to mice grafted with lymph nodes involved by Hodgkin's disease. We postulate that in previous reports, cells resembling RS cells were just binucleated EBV-positive lymphoma blastoid cells rather than actual RS cells.
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PMID:Epstein-Barr virus (EBV)-associated lymphoproliferations in severe combined immunodeficient mice transplanted with Hodgkin's disease lymph nodes: implications of EBV-positive bystander B lymphocytes rather than EBV-infected Reed-Sternberg cells. 863 Apr 8

Soluble isoforms of various adhesion molecules have recently been found in the circulation, but the physiologic effects of such molecules are still unconfirmed. Our earlier study suggests that the serum level of the 70- to 80-kDa form of CD44 (sCD44) parallels the clinical treatment response in patients with lymphoma. In the present study we investigated the origin and the function of sCD44 in non-Hodgkin's lymphoma. Both peripheral blood and tumor lymphocytes were able to shed soluble CD44 in cell culture. In a SCID mouse model, transplanted Burkitt lymphoma (Namalwa) cells transfected with human CD44 shed soluble CD44. In binding studies sCD44 was able to adhere to hyaluronate and fibronectin, and moreover, sCD44 was able to block the binding of hyaluronate to CD44 on the cell surface and to block the binding of lymphocytes to high endothelial venules, suggesting that sCD44 retains its biological activity although it does not contain the cytoplasmic tail. In conclusion, sCD44 is biologically active and is at least partially shed by lymphoma cells in non-Hodgkin's lymphoma patients.
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PMID:Origin and function of circulating CD44 in non-Hodgkin's lymphoma. 905 39


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