Epigenetic modifications in lymphoma: Relevance for pathogenesis and treatment [thesis]

Maria Joosten, Universitätsbibliothek Der FU Berlin, Universitätsbibliothek Der FU Berlin
Lymphomas comprise a very heterogeneous group of haematological cancers that originate from B or T lymphocytes, also known as B and T cells. For a long time, the malignant transformation of B and T cells was mainly associated with genomic alterations, but within the last decade epigenetic modifications were recognized as additional important factors in the pathogenesis of almost all lymphoma entities. Epigenetic mechanisms like DNA methylation and histone modifications regulate gene expression
more » ... ithout altering the underlying DNA sequence. Normally, these processes of gene expression regulation are involved in organ development or cell proliferation. In cancer cells, epigenetic alterations are frequently caused by mutations in chromatin- and/or DNA methylation pattern-modifying enzymes. As a consequence, the accessibility of DNA for transcription factors and thus the respective gene expression is altered. The analysis and understanding of these epigenetic modifications in lymphoma cells is of great clinical relevance since epigenetic modifications can be pharmacologically reversed by using so-called "epidrugs" like DNA methylation inhibitors and histone deacetylation (HDAC) inhibitors. The restoration of the physiological epigenetic landscape might stop uncontrolled cellular proliferation and is thus thought to be a further therapeutic option. However, the determination of biomarkers is essentially required to identify patients who will benefit from treatment with epidrugs. Therefore, the aim of this thesis was (i) to further unravel the role of epigenetic modifications in the pathogenesis of lymphoma and (ii) the identification of markers, which allow a stratification of lymphoma patients eligible for epigenetic therapy with HDAC inhibitors. Regarding (i) the involvement of epigenetic modifications in the pathogenesis of anaplastic large cell lymphoma (ALCL) was in focus. ALCL shows a significant repression of the T-cell expression program despite its T-cell origin. This study identified that mainly two epigeneti [...]
doi:10.17169/refubium-6158 fatcat:xgmuc43gzzhxvefgky4tl2bcca