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Title: Pathogenesis of B-cell post-transplant lymphoproliferative disorders and HIV-associated B-cell lymphomas
Author: Ibrahim, Hazem Ahmed Hamed
ISNI:       0000 0004 2693 9307
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2010
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Genetic and epigenetic alterations as well as viruses such as Epstein Barr virus (EBV) contribute towards the development of immunodeficiency lymphoproliferative disorders (IDLDs). We investigated 66, 25 and 58 cases of post-transplant lymphoproliferative disorders (PTLDs), HIV-B-cell lymphoma (HIV-BCL) and immunocompetent diffuse large B-cell lymphoma (iDLBCL) respectively. Immunohistochemical analysis was used to assess the prevalence of different T-cell subsets, NK cells and plasmacytoid dendritic cells (PDCs) in the microenvironment of these disorders. We used in-situ hybridization to assess the EBV status, fluorescent in-situ hybridization to evaluate common lymphoma-associated gene rearrangements and PCR to determine B- and T-cell clonality, the methylation status of DAP-kinase and SHP1 genes and to identify EBV-genotypes. Our results showed that: 1) EBV is frequently seen in IDLDs with type-A being more prevalent in PTLDs, whilst both types are equally prevalent in HIV-BCLs. Among HIV-BCL, cases associated with type-B-EBV had been HIV- positive for a significantly longer duration compared to those with type-A, 2) Characteristic lymphoma-associated gene rearrangements, apart from c-MYC which showed a significant difference among different groups, are very rare among IDLDs, 3) Aberrant hypermethylation of DAP-k and SHP1 genes is a frequent finding in aggressive BCL and is an early event in the pathogenesis of PTLD, 4) B-PTLDs have significantly higher numbers of CD123- and BDCA-2-positive PDCs as compared to other groups and the numbers are higher in early lesions of PTLD than in the more established lesions, 5) Cases of post-transplant DLBCL have significantly higher numbers of different T cell subsets including regulatory T-cells and NK cells than iDLBCL, and finally 6) Monoclonal T-cell populations, which seem to arise mainly from CD8-positive T-cells, occur frequently in B-PTLDs and they co-exist with the monoclonal B-cell population.
Supervisor: Naresh, Kikkeri ; Stamp, Gordon Sponsor: Government of Egypt
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral