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Query: UMLS:C0001175 (AIDS)
 120,706 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

AIDS (acquired immune deficiency syndrome) and ARC (AIDS-related complex) are associated with a spectrum of lymphoproliferative disorders ranging from lymphadenopathy syndrome (LAS), an apparently benign polyclonal lymphoid hyperplasia, to B cell non-Hodgkin's lymphoma (B-NHL), i.e., malignant, presumably monoclonal B cell proliferations. To gain insight into the process of lymphomagenesis in AIDS and to investigate a possible pathogenetic relationship between LAS and NHL, we investigated the clonality of the B or T lymphoid populations by Ig or T beta gene rearrangement analysis, the presence of rearrangements involving the c-myc oncogene locus, and the presence of human immunodeficiency virus (HIV) sequences in both LAS and B-NHL biopsies. Our data indicate that multiple clonal B cell expansions are present in a significant percentage of LAS (approximately 20%) and B-NHL (60%) biopsies. c-myc rearrangements/translocations are detectable in 9 of our 10 NHLs, but not in any of the LAS cases. However, only one of the B cell clones, identified by Ig gene rearrangements carries a c-myc gene rearrangement, suggesting that only one clone carries the genetic abnormality associated with malignant B cell lymphoma. Furthermore, the frequency of detection of c-myc rearrangements in AIDS-associated NHLs of both Burkitt and non-Burkitt type suggest that the biological alterations present in AIDS favor the development of lymphomas carrying activated c-myc oncogenes. Finally, our data show that HIV DNA sequences are not detectable in LAS nor in NHL B cell clones, suggesting that HIV does not play a direct role in NHL development. Taken together, these observations suggest a model of multistep lymphomagenesis in AIDS in which LAS would represent a predisposing condition to NHL. Immunosuppression and EBV infection present in LAS can favor the expansion of B cell clones, which in turn may increase the probability of occurrence of c-myc rearrangements leading to malignant transformation.
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PMID:Multiple monoclonal B cell expansions and c-myc oncogene rearrangements in acquired immune deficiency syndrome-related lymphoproliferative disorders. Implications for lymphomagenesis. 349 Nov 76

The study of retroviruses now has direct relevance to the understanding of tumorigenesis in humans. This came about through direct demonstration of retroviruses as etiological agents in certain human tumors and through the discovery of a set of cellular genes (onc genes) that may play important roles in normal and abnormal cell growth by their association with certain animal retroviruses. Cellular onc genes are a group of evolutionarily conserved sequences which are homologous to the transforming genes (v-onc) of oncogenic retroviruses. Although their functions in normal cells are largely not known, the sequence homology between cellular onc genes and the transforming v-onc genes is consistent with the idea that neoplastic transformation may, in some cases, be due to abnormal expression of these genes. We have approached this problem by molecular cloning of the human c-onc genes, using these as probes to examine the levels of expression and possible modification of these genes in different neoplastic and normal cells, and by determining their precise locations on the human chromosomes to correlate with known chromosomal alterations in human tumors. Through these studies, we provided evidence for gene amplification and chromosomal translocation as two mechanisms for c-onc activation in tumor cells and implicated the c-myc gene in Burkitt's lymphomas. Human T-cell leukemia virus is a family of related T-lymphotropic viruses isolated from humans. This is the first and thus far the only exogenous human retrovirus identified. A subgroup of this family, human T-cell leukemia virus I, is etiologically associated with a distinct subtype of mature T-cell cancer called adult T-cell leukemia-lymphoma. This association is borne out by extensive seroepidemiology which revealed several regions of the world, including Southwestern Japan, the Caribbean Islands, and Africa, to be endemic; by demonstration of viral sequences clonally integrated in the adult T-cell leukemia cells; and, more remarkably, by the capacity of the virus to transform normal human T-cells in culture and in effect reproduce in vitro some of the in vivo leukemogenic events. Other subgroups that are distantly related to human T-cell leukemia virus I have been obtained from a patient with T-cell hairy cell leukemia and patients with acquired immunodeficiency syndrome. The full disease spectrum of these viruses remains to be determined.
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PMID:Current thoughts on the viral etiology of certain human cancers: The Richard and Hinda Rosenthal Foundation Award lecture. 632 23

The occurrence of HIV associated non-Hodgkin's lymphoma (NHL) is a well recognized event. HIV associated Hodgkin's disease (HD) has also been observed. A unique patient with both entities is described. The patient was a 29 year old homosexual male who developed clinical IIA nodular sclerosis HD in 1985. He was HIV + with CD4/CD8 = 0.2 and his sister had HD 20 years earlier. He received MOPP and had a complete response. In October 1988 he developed weight loss with an abdominal mass and biopsy revealed diffuse small non-cleaved NHL, with bone marrow involvement. This was his first AIDS associated illness. Probes identified clonally rearranged DNA fragments in the J region of IgH chains and clonal rearrangements in the c-myc gene were also observed but EBV sequences could not be demonstrated. He was treated with m-BACOD but died in March 1989. His course was not complicated by opportunistic infection. Possible etiologies for the HD include his HIV status or shared sibling environment. The development of the NHL may have resulted from HIV infection and/or secondary to his treatment for HD. The relationship between the two lymphomas is uncertain and factors other than HIV exposure and its immune dysfunction may have been causal.
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PMID:Hodgkin's disease and non-Hodgkin's lymphoma in an HIV positive patient. 768 28

The authors summarize findings on apoptosis-programmed cellular death, incl. basic data on expression of genes promoting (p53, c-myc, MTS 1 and fas) or inhibiting (bcl-2, bcr-abl) this process. The authors discuss clinical possibilities of controlling apoptosis, in particular in oncology and in autoimmune disease, AIDS, metabolic disorders etc.
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PMID:[Apoptosis--programmed cell death]. 775 84

Lymphoma is one of the defining manifestations of AIDS. Most of these lymphoproliferations are high-grade B-cell non-Hodgkin's lymphoma. Unlike lymphoproliferations that arise in other settings of immunodeficiency, HIV-related lymphomas have a variable association with Epstein-Barr virus (EBV) and also contain alterations in c-myc and p53. EBV infection appears to precede clonal expansion, and its latent expression pattern (Epstein-Barr nuclear antigen1+/Epstein Barr nuclear antigen 2-/latent membrane protein+) is unique among non-Hodgkin's lymphomas. Both EBV types A and B are present in HIV-related lymphomas. Mutations in c-myc include translocations and point mutations. Other altered loci include ras and bcl-6. Although all of these somatic alterations can be detected in lymphomas arising in the general population, their accumulation in a relatively short period (6 to 8 years) after HIV infection suggests an acceleration of underlying mechanisms.
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PMID:Biologic aspects of AIDS-related lymphoma. 782 54

The AIDS-associated lymphomas represent a heterogeneous set of disease processes. The largest histologic subset of lymphomas is the large-cell lymphomas, which represent a spectrum of disease processes ranging from monomorphic monoclonal B-cell proliferations to very polymorphic and polyclonal mixtures of B cells, T cells and macrophages. The next most frequent class of systemic lymphoma are the small non-cleaved cell or Burkitt's-like lymphomas. These are relatively monomorphic, monoclonal malignant B-cell proliferations. The final subset of lymphomas, which are likely to become more common as the AIDS epidemic progresses, are the primary CNS lymphomas, which are expansions of EBV-immortalized B cells. The high incidence of tumor-associated EBV in the CNS lymphomas makes these lesions somewhat analogous to an opportunistic EBV infection. In HIV disease there is a long lag after infection before the appearance of clinical manifestations of impaired T-cell immunity. During this period, both appropriate B-cell proliferation in response to antigen (including the ubiquitous HIV) and abnormal B-cell proliferation (autoimmune, dysregulated) occur as the follicular architecture is disrupted by the virus and potential APC are exposed and/or infected with HIV. The destruction of FDC or the involution of their processes could interfere with the elimination by apoptosis of low-avidity B-cell clones. Antigen-competent B cells with pre-existing chromosomal translocations such as the t(8;14) (c-myc, IgH) would have a selective growth advantage in this setting. Figure 9 shows a schematic representation of prelymphomatous and lymphomagenic events as they are projected to occur. A similar pathogenetic scheme has been postulated for follicular B-cell lymphomas: PCR studies have demonstrated that a pool of t(14;18) (IgH;bcl-2) B-cells are present in lymph nodes featuring follicular hyperplasia. In response to antigen (the evidence favoring antigen drive is extensive hypersomatic mutation in sequences related to binding sites), B cells with the t(14;18) translocation have a selective advantage because the bcl-2 oncogene confers a resistance to apoptosis. Burkitt's lymphomas, particularly sporadic or HIV variants, fulfill at least the key criteria for antigen competence, mainly the presence of surface Ig. The c-myc-associated chromosomal translocational events are likely to occur early during the enzymatic machinations of gene rearrangement. Such B cells would be in the dysregulated cytokine and antigen milieu of HIV disease and ultimately could have a selective advantage. EBV infection of B cells probably requires activation and expression of the CD21 receptor. Furthermore, CD5+ B cells of CLL are refractory to EBV infection.(ABSTRACT TRUNCATED AT 400 WORDS)
AIDS 1994 Aug
PMID:Pathogenesis of AIDS lymphomas. 798 99

We have analyzed 30 cases of high- and intermediate-grade acquired immunodeficiency syndrome-associated non-Hodgkin's lymphoma (AIDS-NHL) for mutations in the c-myc coding region. In addition, in these same tumors, we have sought the presence of mutations in a regulatory region within the first c-myc intron defined by the binding to a factor that inhibits c-myc transcription (MYC intron factor, or mif). Mutations in the c-myc coding region were present in 10 of 16 small noncleaved cell lymphoma (SNCL), but in only 3 of 14 other histologic subtypes tested (0/3 large non-cleaved cell, 2/8 immunoblastic, and 1/3 anaplastic large cell lymphomas). Nineteen of the AIDS-NHLs analyzed contained a c-myc rearrangement and in 10 of these the c-myc gene was mutated in its coding region. In contrast, we could detect a mutation in the coding region in only 2 of 8 AIDS-NHL without a c-myc rearrangement. Mutations in the mif region were detected in 5 of 16 SNCL. Among AIDS-NHL carrying mutations in the c-myc coding region, only 4 carried mutations in the regulatory region. These results suggest that the mutations in the coding region of the c-myc protein may either be a consequence of the translocations involving c-myc, or may be necessary only in tumors where c-myc is deregulated as a result of a c-myc/lg translocation.
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PMID:Mutations in the coding region of c-myc occur frequently in acquired immunodeficiency syndrome-associated lymphomas. 804 69

Burkitt's lymphoma (BL) is a monoclonal lymphoproliferative disorder characterized by the presence of specific chromosomal translocations that involve the c-myc proto-oncogene. Two subtypes of BL exist (endemic and sporadic) that differ in the prevalence of EBV genome expression. Although EBV infection may promote cellular proliferation in endemic BL, little is known about the forces that drive clonal expansion and evolution in the majority of EBV-negative sporadic BL. This study on an EBV-negative sporadic BL cell line derived from an AIDS patient provides evidence that antigenic stimulation may play a role in the development and/or expansion of such tumors. This cell line (BRG-P) contained a series of cellular clones that elaborated both IgM and IgA. Southern blot analyses of the line and its sublines indicated that both the IgM+ and IgA+ cells had identical c-myc and Ig JH gene rearrangements, indicating that they were derived from a common precursor, some of which eventually underwent an isotype switch. Ig VH gene sequence analyses of 21 molecular clones derived from the parental BRG BL line and two of its sublines demonstrated that all the clones used the same VH3 gene. Five unique intraclonal variants were identified at four distinct nucleotide positions (125, 161, 355, 375), which undoubtedly represented somatic mutations. Four of these five mutations occurred within complementary determining regions; all resulted in amino acid replacements. Moreover, an identical G to A nucleotide substitution that resulted in an identical amino acid change occurred at two distinct points in clonal evolution that were separated by the isotype class switch. Thus, the locations and types of the VH gene mutations, together with the occurrence of an isotype switch, are highly suggestive of an ongoing role for Ag stimulation and selection in the evolution of the malignant clone.
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PMID:A potential role for antigen selection in the clonal evolution of Burkitt's lymphoma. 820 54

Acquired immunodeficiency syndrome-associated non-Hodgkin's lymphomas represent a significant and formidable clinical problem. They also represent an important biologic model for investigating the development and progression of high-grade malignant lymphomas and for studying lymphomas that develop in the setting of immune deficiency. A vast majority of non-Hodgkin's lymphomas exhibit clonal immunoglobulin gene rearrangements and, hence, are B-cell neoplasms. Most express B-cell phenotypes, but a minority, predominantly body cavity-based tumors, express indeterminate phenotypes. AIDS-associated non-Hodgkin's lymphomas do not contain HIV. However, approximately 40% of systemic non-Hodgkin's lymphomas, predominantly those with immunoblastic plasmacytoid morphology, and essentially 100% of primary central nervous system AIDS-associated non-Hodgkin's lymphomas contain Epstein-Barr virus. The c-myc protooncogene is rearranged in approximately 80% of systemic cases, predominantly in those with Burkitt's and Burkitt's-like morphology. Point mutations of the ras gene are detectable in approximately 15% of systemic cases. The p53 tumor-suppressor gene is mutated in approximately two thirds of systemic AIDS-associated Burkitt's and Burkitt's-like non-Hodgkin's lymphomas. The retinoblastoma tumor-suppressor gene does not appear to be mutated or deleted in AIDS-associated non-Hodgkin's lymphomas. In summary, various genetic lesions occur in AIDS-associated non-Hodgkin's lymphomas, which appear to vary according to the anatomic site of disease (systemic vs central nervous system vs body cavity) and the histopathology (Burkitt's vs immunoblastic vs large cell). Further active investigation is necessary to determine the role of these and possibly other genetic lesions in AIDS lymphomagenesis.
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PMID:Biologic aspects of AIDS-associated non-Hodgkin's lymphoma. 821 97

From the sera of patients with advanced cancer, a novel factor called SDF (serum-derived factor) was partially purified. SDF was shown to stimulate transcription from the long terminal repeat (LTR) of human immunodeficiency virus type 1 (HIV-1) by transient CAT assay. It did not stimulate gene expression of various control promoters including Rous sarcoma virus, human c-fos, c-myc, c-H-ras and chicken beta-actin genes. The SDF preparation did not contain any detectable TNF-alpha or TNF-beta, and differed in its physicochemical properties from TNFs. We concluded that SDF might be a novel factor associated with the clinical features of advanced cancer. It is speculated that SDF might have some role in disease progression of AIDS as well as in the development of the cachectic conditions in AIDS associated with malignancies.
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PMID:Identification in the sera from patients with advanced cancer of a factor which stimulates gene expression from human immunodeficiency virus type 1. 823 10


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