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ON THE ROAD TO EXCELLENCE IN UNRAVELLING THE (EPI)GENETIC LANDSCAPE OF HEMATOLOGIC NEOPLASMS

Lecture

Lecture entitled ‘Modeling mantle cell lymphoma in mice and therapeutic targeting of its cell-of-origin’ by Tim Pieters, PhD, Ghent University took place.

Abstract: In this NEXT LEVEL seminar, I will discuss advances that were made in the lab of Prof. Pieter Van Vlierberghe in modeling mantle cell lymphoma (MCL) in mice. MCL is an aggressive B cell lymphoma with poor long-term overall survival. Currently, MCL research and development of potential cures is hampered by the lack of good in vivo models. We have modeled events that occur in MCL patients, such as the activation of cell cycle regulator Cyclin D2 (encoded by CCDN2) or the transcription factor SOX11, in mice, and found that overexpression of Ccnd2 or SOX11 is sufficient to drive MCL-like lymphoma in mice. The onset of  MCL-like lymphomas is further accelerated by a B-cell specific loss of the tumor suppressor p53. Finally, we identified B1a cells as the cell-of-origin for murine MCL-like lymphoma and identified MALT1 protease activity as a drugable node downsteam of the BCR signaling pathway.