Pillonel, Vincent. Dissecting the role of histone deacetylases 1, 2, and 6 in Eμ-myc driven B cell lymphoma. 2016, PhD Thesis, University of Basel, Faculty of Science.
Official URL: http://edoc.unibas.ch/diss/DissB_11979
The first, and main part of my thesis work is the study of the functional role of classII Hdac1 and Hdac2 in the Eμ-myc mouse model of B cell lymphoma. We found, that Hdac1 and Hdac2 have a pro-oncogenic roles in both, Eμ-myc tumorigenesis and tumor maintenance. In this study, we reveal for the first time in the Eμ-myc model, that Hdac1 and Hdac2 promote tumorigenesis in a gene dose-dependent manner, with a dominant function of Hdac1. Our findings raise the prospect of using selective HDAC1 (and HDAC2) inhibitors in clinics for the treatment of BL and other B cell lymphomas with Myc deregulation. The results of this work are presented in the form of a publication manuscript: “Histone deacetylase 1 plays a predominant role in Eμ-myc driven B cell lymphoma” (Pillonel et al., Accepted for publication in Scientific Reports).
The second part of my thesis adresses the functional role of Hdac1 and Hdac2 in B cell development. This work was done in collaboration with R.M. Heideman. We could confirm our previous findings that Hdac1 and Hdac2 regulate B cell development in a gene dose-dependent manner, with a dominant function of Hdac1. We show, that Hdac1Δ/Δ;Hdac2Δ/+ mice have abnormal early B cell development. Further preliminary findings provide an insight into the role of Hdac1 and Hdac2 in B cell development, and suggests possible defects in V(D)J recombination.
In the last part of my thesis, I focus on the cytoplasmic classII Hdac6. We dissected the role of Hdac6 in Eμ-myc driven B cell lymphoma. We found, that Hdac6 overexpression accelerates lymphomagenesis, whereas Hdac6 knockout in the germ line may delay tumor development in Eμ-myc mice.
|Advisors:||Matthias, Patrick and Schwaller, Jürg|
|Faculties and Departments:||09 Associated Institutions > Friedrich Miescher Institut FMI > Transcriptional and epigenetic networks and function of histone deacetylases in mammals (Matthias)|
|Bibsysno:||Link to catalogue|
|Number of Pages:||1 Online-Ressource (250 Seiten)|
|Last Modified:||28 Dec 2016 11:57|
|Deposited On:||28 Dec 2016 11:56|
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