Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
 ...
PMID:Biologic aspects of AIDS-related lymphoma. 782 54

AIDS-related non-Hodgkin's lymphomas (AIDS-NHLs) are almost invariably derived from B cells and are grouped into three distinct histologic categories, including small-non-cleaved-cell lymphoma (SNCCL), diffuse large-cell lymphoma (DLCL), and anaplastic large-cell lymphoma (ALCL). In addition, AIDS-NHLs presenting solely as a body cavity effusion are thought to be a peculiar clinicopathologic entity and are defined as body-cavity-based lymphoma (BCBL). At the biologic level, AIDS-related lymphomagenesis is characterized by activation of proto-oncogenes, inactivation of tumor suppressor genes, viral infection of the tumor clone, and deregulated cytokine production. Distinct AIDS-NHL types associate with specific molecular pathways. The first pathogenetic pathway clusters with AIDS-SNCCL, and is characterized by a relatively mild degree of host immunodeficiency. AIDS-SNCCL consistently associates with c-myc rearrangements and p53 inactivation in 100 and 60% of cases, respectively, whereas infection by Epstein-Barr virus (EBV) is restricted to 30% of the cases. Production of high levels of interleukin-10 is an additional peculiar feature of EBV-positive AIDS-SNCCL. The second pathogenetic pathway associates with AIDS-DLCL, which is usually accompanied by marked host immunodeficiency. AIDS-DLCL is characterized by EBV infection in the large majority of cases and by the mutually exclusive presence of bcl-6 rearrangements and c-myc translocations in 40% of the cases. A third pathway characterizes AIDS-BCBL, which associates in virtually all cases with infection by EBV and with the presence of DNA sequences of the recently identified Kaposi sarcoma herpesvirus in the apparent absence of other known genetic lesions. Finally, the pathogenetic features of AIDS-ALCL are still under investigation.
 ...
PMID:AIDS-related non-Hodgkin's lymphomas: molecular genetics, viral infection and cytokine deregulation. 867 42

The incidence of non-Hodgkin's lymphoma is greatly increased in human immunodeficiency virus (HIV)-infected individuals. Most are clinically aggressive B-cell lymphomas exhibiting Burkitt-type, immunoblastic or large-cell morphology. Approximately 80% arise systemically (nodal or extranodal), and the remaining 20% arise in the central nervous system. A small proportion are body cavity-based (primary effusion) lymphomas associated with Kaposi's sarcoma-associated herpesvirus (KSHV) infection. Possible factors contributing to lymphoma development include HIV-induced immunosuppression, chronic antigenic stimulation, and cytokine overproduction. These phenomena are associated with the development of oligoclonal B-cell expansions. The appearance of malignant lymphoma is characterized by the presence of a monoclonal B-cell population displaying a variety of genetic lesions including Epstein-Barr virus (EBV) infections, c-myc gene rearrangement, bcl-6 gene rearrangement, ras gene mutations, and p53 gene mutations/deletions. The number and type of genetic lesions varies according to anatomic site of origin and histopathology. In the case of Burkitt-type lymphoma, virtually 100% exhibit c-myc gene rearrangement, two thirds display p53 gene mutations, one third contain EBV, and none exhibit bcl-6 gene rearrangements. In contrast, in the case of immunoblastic lymphoma, virtually 100% contain EBV, 25% display c-myc gene rearrangements, 20% display bcl-6 gene rearrangements, and few exhibit p53 gene mutations. These findings suggest that more than one pathogenetic mechanism is operational in the development and progression of acquired immunodeficiency syndrome (AIDS)-related lymphoma. Further work is necessary to develop a thorough understanding of the origin and pathogenesis of malignant lymphoma in the setting of HIV infection. AIDS-related lymphoma remains an important biologic model for investigating the development and progression of high-grade non-Hodgkin lymphomas as well as malignant lymphomas that develop in immune-deficient hosts.
 ...
PMID:Molecular pathology of acquired immunodeficiency syndrome-related non-Hodgkin's lymphoma. 904 11

Among patients with congenital and acquired immunodeficiencies, non-Hodgkin's lymphoma (NHLs ) are the most common tumors of the immune system. In the setting of human immunodeficiency virus (HIV) infection, as many as 10% to 20% of people ultimately developed NHLs. These tumors are clinically aggressive, frequently involve extranodal sites, and often exhibit unique features that distinguish them from NHL arising in individuals with other forms of immunosuppression. Important in the development of HIV-associated NHL are cytokines and other factors that induce B-cell proliferation and increase the likelihood of mutations of c-myc, bcl-6, and other tumor-suppressor genes with carcinogenic potential. Specific forms of HIV-associated NHL are linked to expression of Epstein-Barr virus (EBV)-latent proteins; the newly described DNA virus, Karposi's sarcoma-associated herpesvirus/human herpesvirus-8 (KSHV/HHV-8); and perhaps HIV. Elucidation of the factors that contribute to the high incidence of NHL among patients infected with HIV provides insights into important elements of lymphomagenesis.
 ...
PMID:Epidemiology and pathogenesis of AIDS-related lymphomas. 968 78

To evaluate the value of Epstein-Barr virus DNA (EBV-DNA) assay in cerebrospinal fluid (CSF) for monitoring the response to treatment in acquired immunodeficiency syndrome-related primary central nervous system lymphoma (AIDS-PCNSL), 9 human immunodeficiency virus-infected patients with biopsy-proven AIDS-PCNSL who underwent multimodal therapy were investigated for EBV-DNA detection in CSF by semiquantitative nested polymerase chain reaction (PCR). Tumoral tissue expression of bcl-6 oncogene protein and of EBV-encoded latent membrane protein (LMP-1) was also investigated. The 2 patients who had a response to chemotherapy showed a reduction of mean EBV-DNA concentration values after chemotherapy and displayed a large noncleaved morphology and a BCL-6+/LMP-1- phenotype. Conversely, the 4 patients with progressive disease after chemotherapy showed increasing mean values of EBV-DNA and displayed an immunoblastic morphology and a BCL-6-/LMP-1+ phenotype. No significant changes were observed for patients with stable disease. EBV-DNA burden reduction was significantly associated with prolonged survival. These results suggest that EBV-DNA monitoring might be helpful in predicting response to chemotherapy and in segregating distinct biological and prognostic categories of AIDS-PCNSL.
 ...
PMID:Epstein-Barr virus in monitoring the response to therapy of acquired immunodeficiency syndrome-related primary central nervous system lymphoma. 998 31

The incidence of lymphoproliferative disease is significantly higher in individuals who have congenital, acquired, or iatrogenically induced immunodeficiency. The immunodeficiency-associated lymphoproliferative disorders are clinically and pathologically heterogeneous, are of variable clonal composition, and vary according to the immunodeficiency syndrome. Nonetheless, they share several features, including frequent origination in or involvement of extranodal sites, diffuse aggressive histology, B-cell lineage derivation, association with the Epstein-Barr virus (EBV), and, often, rapid clinical progression. Reactive and atypical lymphoid hyperplasias and malignant lymphomas occur in association with congenital (primary) immunodeficiency. Post-transplantation lymphoproliferative disorders are often comprised of a polymorphic cell population, making it difficult to identify their benign or malignant nature by histopathologic criteria alone. Recent studies suggest that they are divisible into plasmacytic hyperplasias, polymorphic lymphoproliferative disorders, and malignant lymphomas. The plasmacytic hyperplasias are polyclonal and generally regress spontaneously following withdrawal of immunosuppression. The malignant lymphomas are monoclonal, possess a variety of genetic alterations, and generally progress despite aggressive therapy. The polymorphic lymphoproliferative disorders are also monoclonal but display variable clinical behavior, their progression apparently correlating with bcl-6 gene mutation. Non-Hodgkin's lymphoma (NHL) is the second most common AIDS-related neoplasm and an AIDS-defining illness. AIDS-related NHLs are divisible by anatomic site of origin into systemic (nodal/extra nodal), primary central nervous system, and body cavity-based (primary effusion) lymphomas; and by histopathology into Burkitt's and Burkitt's-like lymphoma, large cell lymphoma, and large cell immunoblastic (plasmacytoid) lymphoma More than 90% are monoclonal B-cell neoplasms. The primary effusion lymphomas contain the Kaposi's sarcoma-associated herpesvirus. Multiple molecular pathways appear to operate in AIDS lymphomagenesis and some may be preferentially associated with specific histopathologic categories or anatomic sites of origin. In conclusion, the immunodeficiency-associated lymphoproliferative disorders often represent a significant diagnostic problem requiring correlative analysis of the clinical behavior of the patient with the histopathology, immunophenotype, clonal composition, viral content, and genetic alterations of the lymphoproliferative disorder. They also represent an important biological model for studying the development and progression of lymphoid neoplasia
 ...
PMID:Immunodeficiency-associated lymphoproliferative disorders. 1007 43

Post-transplant lymphoproliferative disorders (PTLD) share many of the features of human immunodeficiency virus (HIV)-related lymphomas, although important differences exist. PTLD ranges from hyperplastic lesions to aggressive lymphoma or multiple myeloma histology. The coexistence of multiple clones, and the strong association with the Epstein-Barr virus (EBV), represent a uniquely different mechanism for lymphomagenesis when compared with de novo lymphoma. The risk of PTLD increases as the duration of immunodeficiency lengthens, with unusual, newly described entities arising after prolonged immunosuppression. The risk is also strongly influenced by the specific anti-T-cell therapies used to prevent graft rejection, providing insight into the nature of immune surveillance. The presence or absence of bcl-6 mutations may be predictive of the reversibility of the PTLD with reduction in immunosuppressive therapy. The use of cytotoxic agents has been complicated by problems similar to those encountered with HIV-related lymphomas, but can nonetheless be very effective. Long-term remission has been achieved with anti-CD21 and anti-CD24 antibodies, although these have not been equally effective for all categories of PTLD. In vitro-expanded EBV-specific T cells have been effective both as treatment and as prophylaxis in the setting of PTLD occurring after marrow transplantation. EBV viral load measurement correlates with the emergence of PTLD, and may make clinical trials of screening, prophylaxis, or early intervention possible.
 ...
PMID:Transplantation-related lymphoproliferative disorder: a model for human immunodeficiency virus-related lymphomas. 1095 Mar 66

Post-transplant lymphoproliferative disorders (PTLDs) comprise a histologic spectrum, ranging from hyperplastic-appearing lesions to frank non-Hodgkin's lymphoma or multiple myeloma histology. Multiple clones may coexist, each representing a discrete lymphomagenic event, a situation that is unique to immunodeficiency states. The incidence varies from 1% in renal recipients to 5% in heart recipients, but can be markedly increased by the use of anti-T-cell therapies or by T-cell depletion in bone marrow transplantation. PTLD continues to arise, even many years after transplantation, and late T-cell lymphomas have recently been recognized. Pretransplant Epstein-Barr virus (EBV) seronegativity increases risk to as high as 30%-50%. 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 for interferon alfa 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 associate 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 the acquired immunodeficiency syndrome setting.
 ...
PMID:Post-transplant lymphoproliferative disorders: implications for acquired immunodeficiency syndrome-associated malignancies. 1115 5

Simian AIDS-related lymphomas (sARL) of cynomolgus monkeys infected with a simian immunodeficiency virus (SIVsm) were studied in relation to growth in severe combined immunodeficient (SCID) mice, karyotype abnormalities, and DNA sequence of the first noncoding region of the Bcl-6 gene. The tumors were diffuse large B cell lymphomas and expressed a simian homolog to Epstein-Barr virus (HVMF-1) in 12 of 13 primary tumors and corresponding cell lines. A tested cell line was tumorigenic in SCID mice. Tumors in the SCID mice showed cell growth features similar to those in the original lymphoma, suggesting that no subpopulation with growth advantage was selected for in the mice. Spectral karyotype analysis of sARL cell lines showed normal cytogenetic features except for a trisomy of monkey chromosome 2 (corresponding to human chromosomes 7 and 21) in two of five sARL lines, which was not recovered in SCID tumors established from the same cell line. Sequence analysis of a Bcl-6 gene fragment showed sequence variations indicative of population polymorphism(s) in 10 of 13 sARLs, and no evidence of Bcl-6 mutations. Thus Bcl-6 mutations in the first noncoding region are irrelevant for sARL development in cynomolgus monkeys and for tumorigenicity of sARL cell lines. We also demonstrate that no cytogenetic alterations are needed for the development of highly aggressive lymphomas in the SIV-immunosuppressed host.
 ...
PMID:Simian AIDS-related lymphoma growth in severe combined immunodeficiency mice is independent of karyotypic abnormalities or Bcl-6 mutations. 1189 40

Primary effusion lymphoma (PEL) is recognized as a unique clinicopathological entity associated with human herpesvirus 8 (HHV-8), and it occurs almost exclusively in human immunodeficiency virus (HIV)-infected individuals. In the majority of PEL cases, Epstein-Barr virus (EBV) has been found in the tumor cells as well. We describe here an elderly HIV seronegative female patient with PEL in the pleura and pericardium not associated with HHV-8 or EBV. Cytologic examinations of the pleural effusion revealed large lymphoma cells with immunophenotypes positive for CD8, CD10, CD19, CD20, CD22, CD24, CD45, and HLA-DR but negative for CD30 and surface immunoglobulin. Chromosome analysis showed complicated abnormalities including add(3)(q27). Immunoglobulin gene rearrangement was detected by Southern blotting; however, c-myc, Bcl-2, and Bcl-6 genes were not rearranged. The patient was treated with a modified CHOP (cyclophosphamide, hydroxydoxorubicin, oncovine, and prednisolone) regimen, and achieved remission. Recurrence of PEL in the pericardium as effusion lymphoma was found 3 months after the discontinuation of CHOP. After approximately 1 year of intermittent multiagent salvage therapy for pericardial recurrences, a treatment that resulted in a partial response, 3 cycles of monotherapy with sobuzoxane were administered. At the time of this report the patient had been free from PEL for more than 18 months without chemotherapy.
 ...
PMID:Durable remission by sobuzoxane in an HIV-seronegative patient with human herpesvirus 8-negative primary effusion lymphoma. 1516 97


1 2 Next >>