Maria Bro Kloster

PhD thesis – Maria Bro Kloster, 26 October 2012

On Friday 26 October 2012, M.Sc.Eng. (Medical Biotechnology) Maria Bro Kloster, Department of Haematology, defended her PhD thesis with the title: “Alternative Transcription Start Sites in Transcription Factors in Normal B-cell Subpopulations and Diffuse Large B-cell Lymphoma”.

About 1000 new cases of lymphoma are diagnosed in Denmark every year, of which non-Hodgkin lymphoma (NHL) is the most frequent subtype. About 400 of newly diagnosed NHL are classified as diffuse large B-cell lymphoma (DLBCL). DLBCL is a highly heterogeneous disease, not only with respect to clinical information and outcome, but also with respect to biological analysis of morphology, immunohistochemistry, cytogenetics, and gene expression.

We believe that alternative transcription starts sites in genes encoding transcription factors have an important role as determinants of the biogenesis of both the normal B-cell differentiation and malignant B-cell development. This PhD project, therefore, focuses on understanding the heterogeneity based on the cellular hierarchy and the involvement of alternative transcription start sites of genes encoding transcription factors in the normal B-cell differentiation and lymphomagenesis.

We found that usage of alternative transcription factors is common during the normal B-cell differentiation, and thus, B-cells have developed a complexity to fine-tune the functional diversity of transcription factors in a cell-type specific manner during the normal B-cell differentiation.

Furthermore, a limited number of transcription factors are deregulated in DLBCL tumour tissues with mRNA expression levels of prognostic impact, supporting their involvement in the pathogenesis of DLBCL. The tumour cell concentration is an important factor variable when interpreting gene expression profiles for both microarray- and next generation sequencing-based analyses.

Evaluation committee:

  • Sabina Sevcikova, M.Sc., PhD, Barak Myeloma Group, Department of Pathological Physiology, Faculty of Medicine, Masaryk University, Czech Republic
  • Mads Thomassen, M.Sc., PhD, Institute for Human Genetics, Odense University Hospital, Denmark
  • Associate Professor, Steffen Junker, PhD, Department of Biomedicine – Department of Human genetics, Aarhus University, Denmark

Supervisors:

  • Associate Professor, Karen Dybkær, Department of Haematology, Aalborg Hospital, Aarhus University, Denmark
  • Professor, Hans E. Johnsen, Department of Haematology, Aalborg Hospital, Aarhus University, Denmark

Time:

  • 26 October 2012, at 13.00 p.m.

Place:

  • In the auditorium at Aalborg Science and Innovation Center, Aalborg Hospital, Aarhus University Hospital