Differential regulation of Blimp1 isoforms by the Epstein-Barr virus; implications for virus persistence and the pathogenesis of EBV-associated lymphomas

Konference: 2010 6. sympózium a workshop molekulární patologie a histo-cyto-chemie

Kategorie: Nádorová biologie/imunologie/genetika a buněčná terapie

Téma: Keynote lectures of invited speakers

Číslo abstraktu: 011

Autoři: Mgr. Kateřina Vrzalíková; M. Vockerodt; Sarah Leonard; prof. MUDr. Zdeněk Kolář, CSc.; Ciaran Woodman; Prof. Paul G. Murray

The Epstein-Barr virus (EBV) is associated with several types of B cell lymphoma, which include Burkitt˘Ąs lymphoma (BL) and Hodgkin˘Ąs lymphoma (HL). An important pathogenic event in these cancers is the suppression of virus replication which would otherwise result in tumour cell apoptosis. Because the induction of virus replication in EBV-infected non-malignant B cells is intimately linked to their differentiation to plasma cells, we have asked if the physiological signals which drive normal B cell differentiation are absent in EBV-infected lymphoma cells. We have focussed on BLIMP1, a transcription factor which exists as two major isoforms; BLIMP1Ąá, which is required for normal plasma cell differentiation, and BLIMP1©¬ which has impaired ability to repress gene transcription and is highly expressed in myeloma cell lines. We have shown that BUMPIct expression: is low in EBV-infected BL and HL cells; can be down-regulated by EBV infection of primary B cells; and, when introduced ectopically into EBV-infected primary B cells or BL cells, leads to induction of the virus replicative cycle. We have also shown that EBV infection up-regulates BLIMP1©¬ expression, an effect that is associated with hypo-methylation of the BLIMP1©¬-specific promoter. Taken together our results support an important role for the differential regulation of the BLIMP1 isoforms in the pathogenesis of EBV-associated lymphomas.

Datum přednesení příspěvku: 23. 4. 2010