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Silencing immunoglobulin gene enhancers as a potential treatment strategy for multiple myeloma

Multiple myeloma is a bone marrow malignancy characterized by the presence of monoclonal plasma cells. In 50-75% of myeloma patients, chromosome translocations at the IgH locus are observed, which result in overexpression of oncogenes from the translocated chromosome due to linkage with the IgH enhancers. IgH enhancer activity is mediated by the B cell-specific transcription factors Bob1 and Oct2. We hypothesized that inhibiting the IgH enhancer, through inhibition of Bob1 and Oct2, is a potential therapeutic strategy for translocation-positive myeloma. The expression and prognostic value of Bob1 and Oct2 in myeloma patient samples were assayed. High Bob1 expression was associated with increased survival, whereas high Oct2 expression was associated with reduced survival. In a t(4;14) myeloma cell line, Bob1 inhibition led to decreased expression of the translocated oncogene, FGFR3; however, this did not lead to decreased proliferation or increased apoptosis. To fully understand the roles of Bob1 and Oct2 in myeloma, further research is required. / Experimental Oncology

Identiferoai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:AEU.10048/445
Date11 1900
CreatorsToman, Inka
ContributorsReiman, Tony (Oncology), Hitt, Mary (Oncology), McDermid, Heather (Biological Sciences)
Source SetsLibrary and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada
LanguageEnglish
Detected LanguageEnglish
TypeThesis
Format4921739 bytes, application/pdf

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