Gene/Protein Disease Symptom Drug Enzyme Compound
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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)

Patients with X-linked lymphoproliferative (XLP) disease are characterized by extreme vulnerability to Epstein-Barr virus (EBV). Following infection with EBV, affected males develop fatal infectious mononucleosis (IM), hypogammaglobulinemia (H), or non-Hodgkin's lymphoma (NHL). In addition, hyper IgM, red cell aplasia, necrotizing lymphoid vasculitis (NLV), and aplastic anemia occur rarely. The recent use of DNA restriction fragment length polymorphism (RFLP) probes in linkage with the XLP gene now permit detection of affected males prior to primary EBV infection. We have measured immunoglobulin class and subclass levels in sera from EBV-negative males who were either positive or negative for the XLP genotype by RFLP analysis. Elevated IgA or IgM and/or variable deficiency of IgG, IgG1, and IgG3 occurred in the sera of 13/13 RFLP-positive, EBV-negative males. No consistent abnormalities were noted in 14 RFLP-negative, EBV-negative males. We conclude that the immune defect in XLP is not solely EBV-specific, although EBV is responsible for most of the morbidity and all of the mortality. Further, serial measurement of Ig levels may provide information regarding status of EBV-negative males at risk where RFLP analysis is uninformative or in families where sporadic cases of fatal IM, acquired hypogammaglobulinemia or NHL have occurred, but wherein the genotype of XLP cannot be documented.
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PMID:Immunoglobulin class and subclass deficiencies prior to Epstein-Barr virus infection in males with X-linked lymphoproliferative disease. 168 54

An increased incidence of malignant tumors has long been recognized in patients with primary immune defects such as the X-linked lympho-proliferative syndrome or the Wiskott Aldrich syndrome and has recently become a major concern also in cases with acquired immunodeficiency. The latter may be induced by cytostatic therapy for cancer, extended immunosuppression following organ transplantation or HIV infection. The spectrum of secondary cancers is, however, different within these three groups of secondary immune defects with acute myeloid leukemia being the most common malignant disease after cytostatic therapy, with skin or lip cancer followed by non-Hodgkin's lymphoma as the prevalent malignancies after organ transplantations and Kaposi sarcoma and non-Hodgkin's lymphoma as the predominant cancers associated with HIV infection. The pathogenesis of Kaposi sarcoma and non-Hodgkin's lymphoma is possibly related to viral infections by cytomegalovirus and Epstein-Barr virus inducing an increased proliferation and possibly the coactivation of transforming genes of oncogenic potential. In AIDS patients Kaposi sarcoma is diagnosed in up to 40% of homosexual men while the other risk groups are less frequently involved. 4-10% of HIV infected patients experience non Hodgkin's lymphoma predominantly of B-cell type and intermediate or high grade malignancy with frequent extranodal manifestations. Other types of tumors occur at a substantially lower frequency and are not clearly related to the HIV infection. The overall survival of patients suffering from malignant tumors in the state of immunodeficiency is poor and the possibilities for therapeutic intervention are limited by the risk of accelerating the pre-existing suppression of defense mechanisms.
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PMID:What's new in malignant tumors in acquired immunodeficiency disorders? 269 23

X-linked lymphoproliferative disease (XLP) is a rare genetic syndrome that continues to serve as a useful model to understand more broadly the role of immunodeficiency and the pathogenetic mechanisms for the spectrum of Epstein-Barr virus (EBV)-induced diseases to which XLP is predisposed. Apart from XLP, EBV infection is related to the high frequency of non-Hodgkin's lymphoma in children with various primary immune deficiency diseases and in allograft recipients. More recently, EBV has been implicated in several lymphoproliferative diseases in individuals with acquired immune deficiency syndrome. Studies thus far on patients with XLP suggest that immune deficiency is a major determinant of these diseases. Additional molecular aberrations must be necessary in the pathogenesis of lymphoma to convert polyclonal to monoclonal disease.
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PMID:X-linked lymphoproliferative syndrome provides clues to the pathogenesis of Epstein-Barr virus-induced lymphomagenesis. 285 88

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

We report the occurrence of X-linked lymphoproliferative disease (XLP) in two brothers in a Malaysian family. In this disorder, a primary Epstein-Barr virus (EBV) infection is followed by an abnormal proliferation of transformed B-cells that cannot be controlled by suppressor T-cells, leading to the development of deranged immune function. This results in fatal infectious mononucleosis, acquired hypogammaglobulinaemia, virus-infected haemophagocytic syndrome and non-Hodgkin's lymphoma. The diagnosis should be considered when there is a family history of any male having a fulminant course of infectious mononucleosis, an otherwise benign disease. Early diagnosis is important as bone marrow transplantation is the only curative option in this disorder.
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PMID:Two brothers in a Malaysian family with X-linked lymphoproliferative disease--a case report. 894 43

Therapy-related acute myelogenous leukemia and myelodysplastic syndrome (t-AML/MDS) are being reported with increasing frequency as a complication of ABMT for Hodgkin's disease and non-Hodgkin's lymphoma. At present there is no method available to predict who is at risk or is destined to develop this nearly universally fatal disorder. We therefore investigated whether clonal growth of cells is predictive of the development of t-AML/MDS. In a patient who developed secondary AML/MDS 18 months after ABMT, X-linked clonality analysis at the human androgen receptor locus was performed on serial banked samples, and documented transition from polyclonal to clonal hematopoiesis. Clonal cells could be identified 6 months after transplant (1 year prior to the diagnosis of t-AML/MDS), at a time when there was no morphologic or clinical evidence of disease. Clonality analysis can be predictive of the development of t-AML/MDS after ABMT and may offer important insights into associated risk factors and strategies to minimize the risk of t-AML/MDS.
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PMID:Prediction of therapy-related acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS) after autologous bone marrow transplant (ABMT) for lymphoma. 929 68

A recently described atypical myeloproliferative disorder is invariably associated with reciprocal translocations involving 8p11-12. The most common rearrangement is a t(8;13)(p11;q11-12). Here we determine that this translocation results in the fusion of the fibroblast growth factor receptor 1 gene (FGFR1), a member of the receptor tyrosine kinase family at 8p11, to a novel gene at 13q11-12 designated RAMP . The predicted RAMP protein exhibits strong homology to the product of a recently cloned candidate gene for X-linked mental retardation, DXS6673E . We also provide the first report of a novel, putative metal-binding motif, present as five tandem repeats in both RAMP and DXS6673E. RT-PCR detected only one of the two possible fusion transcripts, encoding a product in which the N-terminal 641 amino acids of RAMP become joined to the tyrosine kinase domain of FGFR1. Receptor tyrosine kinases are not commonly involved in the formation of tumour-specific fusion proteins. However, the previous reports of involvement of receptor tyrosine kinases in fusion proteins in non-Hodgkin's lymphoma, chronic myelomonocytic leukaemia and papillary thyroid carcinoma described similar rearrangements. By analogy with these, we propose that the RAMP-FGFR1 fusion product will contribute to progression of this myeloproliferative disorder by constitutive activation of tyrosine kinase function.
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PMID:The t(8;13)(p11;q11-12) rearrangement associated with an atypical myeloproliferative disorder fuses the fibroblast growth factor receptor 1 gene to a novel gene RAMP. 949 16

We present two male siblings suffering from recurrent manifestations of B-cell non-Hodgkin's lymphoma (NHL) and recurrent infections of the lower respiratory tract associated with bronchiectasis. Immunodeficiency could not be demonstrated by any laboratory investigation. In both patients, lymphomas developed without evidence for Epstein-Barr virus (EBV) infection, i.e. no antibody response to EBV-specific antigens, negative EBV-PCR (polymerase chain reaction) in peripheral blood cells, and absence of latent membrane protein (LMP) and EBV-encoded RNA (EBER) in lymphoma cells. Molecular analysis of the SH2D1A, the gene for X-linked lymphoproliferative disease (XLP) led to the identification of a deletion in the first exon in both patients. Therefore, we postulate that the genetic defect and the following dysregulation of the B-/T-cell interaction rendered these patients susceptible to the early onset of B-cell NHL and that EBV infection is not an obligate prerequisite.
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PMID:Recurrent B-cell non-Hodgkin's lymphoma in two brothers with X-linked lymphoproliferative disease without evidence for Epstein-Barr virus infection. 1069 68

X-linked lymphoproliferative (XLP) syndrome is a rare primary immune-deficiency disorder caused by mutations of the SH2D1A or XIAP genes. Males with the disorder are usually in good health until contracting Epstein-Barr virus (EBV) whereupon the majority of patients die from fulminant infectious mononucleosis, lymphoma or hypogammaglobulinaemia. This report describes a female carrier with an XLP phenotype who was retrospectively identified after her grandson died from the disorder. Subsequent genetic testing identified the patient's mother and affected maternal grandmother as XLP carriers. The family's medical records were significant. The proband had lymphoma at ages 2 and 8 and made a full recovery following treatment. Both the maternal grandmother and uncle died of non-Hodgkin's lymphoma. We were concerned that the XLP carrier mother may be predisposed to lymphoma if the normal X chromosome is skewed towards inactivation. The human androgen receptor assay detected random X chromosome inactivation in the carrier mother. EBV was not detected in the lymphoma tissues of the proband and his grandmother, confirming previous findings that EBV is not always associated with lymphoma in XLP. More significantly, our study highlights the importance of identifying XLP in families with a high incidence of lymphoma.
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PMID:Follicular lymphoma in a X-linked lymphoproliferative syndrome carrier female. 1870 45

Lymphoma is seen in up to 30% of patients with X-linked lymphoproliferative disease (XLP), but cerebral vasculitis related with XLP after cure of Burkitt lymphoma is rarely reported. We describe a case of a 5-year-old boy with XLP who developed cerebral vasculitis two years after cure of Burkitt lymphoma. He had Burkitt lymphoma at the age of 3 years and received chemotherapy (non-Hodgkin's lymphoma-Berlin-Frankfurt-Milan-90 protocol plus rituximab), which induced complete remission over the following two years. At the age of 5 years, the patient first developed headache, vomiting, and then intellectual and motorial retrogression. His condition was not improved after anti-infection, dehydration, or dexamethasone therapy. No tumor cells were found in his cerebrospinal fluid. Magnetic resonance imaging showed multiple non-homogeneous, hypodense masses along the bilateral cortex. Pathology after biopsy revealed hyperplasia of neurogliocytes and vessels, accompanied by lymphocyte infiltration but no tumor cell infiltration. Despite aggressive treatment, his cognition and motor functions deteriorated in response to progressive cerebral changes. The patient is presently in a vegetative state. We present this case to inform clinicians of association between lymphoma and immunodeficiency and explore an optimal treatment for lymphoma patients with compromised immune system.
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PMID:Lymphoma and cerebral vasculitis in association with X-linked lymphoproliferative disease. 2381 55


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