1,721,127 research outputs found
MOLECULAR PATHOPHYSIOLOGY OF INDOLENT LYMPHOMA
No full textIndolent lymphomas are a markedly heterogeneous group of lymphoproliferative disorders including B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma, lymphoplasmacytoid lymphoma, follicular lymphoma, mantle cell lymphoma and mucosa-associated lymphoid tissue (MALT) lymphoma. The molecular pathophysiology of indolent lymphoma is characterized by distinct genetic pathways which selectively associate with different clinico-pathologic categories of the disease. At diagnosis, B-cell chronic lymphocytic leukemia frequently display deletions of 13q14, trisomy 12 and alterations of the ATM gene, whereas evolution to Richter's syndrome is associated with disruption of p53. Lymphoplasmacytoid lymphoma carries t(9;14) (p13;q32) in approximately 50% of cases, leading to the deregulated expression of the PAX-5 gene. Follicular lymphoma consistently harbors rearrangement of BCL-2. With time, a fraction of follicular lymphoma accumulates mutations of p53 and of p16 and evolves into a high grade lymphoma. MALT-lymphoma frequently associates with alterations of API2/MLT and, in some cases, of p53, BCL-6 and BCL-10. Studies of genotypic and phenotypic markers of histogenesis have shown that mantle cell lymphoma and a fraction of B-CLL/SLL derive from naive B-cells, whereas follicular lymphoma, lymphoplasmacytoid lymphoma and MALT-lymphoma originate from germinal center (GC) or post-GC B-cells. The identification of distinct genetic categories of indolent lymphoma may help in the therapeutic stratification of these disorders. In addition, genetic lesions of indolent lymphoma provide useful molecular markers for disease monitoring by high sensitivity techniques
Ethic and Biobanks
Full text linkThe bioethical issues faced by a population and disease biobank are addressed in the light of three challenges. The first concerns the adoption of strategies to improve and maintain the quality of biological samples and a management system based on the best standard operating procedures. The essential value of a biobank lies in transforming ‘residual biological materials’ into essential information to improve the health of the population. Research is ‘ethical’ if it is of good quality. The second challenge, which is central to a population biobank, is to match the ‘trust’ of the citizens with the reliability of ‘participatory’ governance. A biobank can fulfil its mission as a ‘service unit’ through the involvement of all the relevant actors: citizens, researchers, and public and private stakeholders. The third challenge is to interpret the shift from the paradigm of ‘property rights’ to the different paradigm of ‘personality rights’. Citizens’ privacy must be understood not as a ‘limitation’ but as a ‘resource’, capable of strengthening research that respects the dignity of the individual, while at the same time being able to answer the increasing number of questions imposed by public and individual health
THE MOLECULAR BASIS OF AIDS-RELATED LYMPHOMAGENESIS
No full textAcquired immunodeficiency syndrome (AIDS)-related lymphomas consistently display a B-cell phenotype and are histogenetically related to germinal center (GC) or post-GC B cells in the overwhelming majority of cases. The pathogenesis of AIDS-related lymphoma is a multistep process involving factors provided by the host, as well as alterations intrinsic to the tumor one. Host factors involved in AIDS-related lymphomagenesis include reduced immunosurveillance particularly against Epstein-Barr virus (EBV)-infected B cells, human immunodeficiency virus (HIV)-induced alteration of endothelial functions, B-cell stimulation and selection by antigen, HIV-induced deregulation of several cytokine loops, and possibly the host's genetic background. The molecular pathways of viral infection and lesions of cancer related genes associated with AIDS-related lymphoma vary substantially in different clinicopathologic categories of the disease and highlight the marked degree of biological heterogeneity of these lymphomas. Although the reasons for the heterogeneity of AIDS-related lymphoma are not totally clear, it is generally believed that the host's background selects for which specific molecular pathway of AIDS-related lymphoma is activated in a given patient
Post-transplant lymphoproliferative disorders: molecular basis of disease histogenesis and pathogenesis
No full textPost-transplant lymphoproliferative disorders (PTLD) represent a serious complication of solid organ and allogeneic bone marrow transplantation. PTLD generally display B-cell lineage derivation, involvement of extranodal sites, aggressive histology and clinical behaviour, and frequent association with EBV infection. The occurrence of IgV mutations in the overwhelming majority of PTLD documents that malignant transformation targets germinal centre (GC) B-cells and their descendants both in EBV-positive and EBV-negative cases. Analysis of phenotypic markers of B-cell histogenesis, namely BCL6, MUM-1 and CD138, allows further distinction of PTLD histogenetic categories. PTLD expressing the BCL6(+)/MUM1(+/-)/CD138(-) profile reflect B-cells actively experiencing the GC reaction and comprise diffuse large B-cell lymphoma (DLBCL) centroblastic and Burkitt lymphoma. PTLD expressing the BCL6(-)/MUM1(+)/CD138(-) phenotype putatively derive from B-cells that have concluded the GC reaction and comprise the majority of polymorphic PTLD and a fraction of DLBCL. A third group of PTLD is reminiscent of post-GC and pre- terminally differentiated B-cells that show the BCL6(-)/MUM1(+)/CD138(+) phenotype and are morphologically represented by either polymorphic PTLD or DLBCL immunoblastic. The molecular pathogenesis of PTLD involves infection by oncogenic viruses, namely Epstein-Barr virus, as well as genetic or epigenetic alterations of several cellular genes. At variance with lymphoma arising in immunocompetent hosts, whose genome is relatively stable, a fraction of PTLD are characterized by microsatellite instability as a consequence of defects in the DNA mismatch repair mechanism. Apart from microsatellite instability, molecular alterations of cellular genes recognized in PTLD include alterations of c-MYC, BCL-6, p53, DNA hypermethylation, and aberrant somatic hypermutation of proto-oncogenes
POST-TRANSPLANT LYMPHOPROLIFERATIVE DISORDERS: ROLE OF VIRAL INFECTION, GENETIC LESIONS AND ANTIGEN STIMULATION IN THE PATHOGENESIS OF THE DISEASE
No full text<p class="MsoNormal" style="text-align: justify; line-height: 200%; margin: 0cm 0cm 0pt; mso-layout-grid-align: none;"><span style="font-family: ";Arial";,";sans-serif";; mso-ansi-language: EN-US;" lang="EN-US"><span style="font-size: small;">Post-transplant lymphoproliferative disorders (PTLD) are a life-threatening complication of solid organ transplantation or, more rarely, hematopoietic stem cell transplantation. The majority of PTLD is of B-cell origin and associated with Epstein–Barr virus (EBV) infection. PTLD generally display involvement of extranodal sites, aggressive histology and aggressive clinical behavior. The molecular pathogenesis of PTLD involves infection by oncogenic viruses, namely Epstein-Barr virus, as well as genetic or epigenetic alterations of several cellular genes. At variance with lymphoma arising in immunocompetent hosts, whose genome is relatively stable, a fraction of PTLD are characterized by microsatellite instability as a consequence of defects in the DNA mismatch repair mechanism. Apart from microsatellite instability, molecular alterations of cellular genes recognized in PTLD include alterations of cMYC, BCL6, TP53, DNA hypermethylation, and aberrant somatic hypermutation of protooncogenes. The occurrence of IGV mutations in the overwhelming majority of PTLD documents that malignant transformation targets germinal centre (GC) B-cells and their descendants both in EBV–positive and EBV–negative cases. Analysis of phenotypic markers of B-cell histogenesis, namely BCL6, MUM1 and CD138, allows further distinction of PTLD histogenetic categories. PTLD expressing the BCL6+/MUM1+/-/CD138- profile reflect B-cells actively experiencing the GC reaction, and comprise diffuse large B-cell lymphoma (DLBCL) centroblastic and Burkitt lymphoma. PTLD expressing the BCL6-/MUM1+/CD138- phenotype putatively derive from B-cells that have concluded the GC reaction, and comprise the majority of polymorphic PTLD and a fraction of DLBCL immunoblastic. A third group of PTLD is reminiscent of post-GC and preterminally differentiated B-cells that show the BCL6-/MUM1+/CD138+ phenotype, and are morphologically represented by either polymorphic PTLD or DLBCL immunoblastic.</span></span></p>
HIGHLY ACTIVE ANTIRETROVIRAL THERAPY IN HUMAN HERPESVIRUS-8 RELATED BODY-CAVITY-BASED LYMPHOMA
No full text
GENETIC PATHWAYS AND HISTOGENETIC MODELS OF AIDS-RELATED LYMPHOMAS
No full textAcquired immunodeficiency syndrome (AIDS)-related lymphomas consistently display a B-cell phenotype and are histogenetically related to germinal centre or post-germinal centre B cells in the overwhelming majority of cases. The pathogenesis of AIDS-related lymphoma is a multistep process involving factors provided by the host as well as alterations intrinsic to the tumour clone. The molecular pathways of viral infection and lesions of cancer-related genes associated with AIDS-related lymphomas vary substantially in different clinicopathological categories of the disease and highlight the marked degree of biological heterogeneity of these lymphomas
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