Epigenetic regulation in normal and malignant hematopoisesis

Research output: Types of ThesisDoctoral ThesisInternal

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Every day, the hematopoietic system produces billions of blood cells of multiple lineages, with essential functions in nutrient transport and immune defense. This process is strictly regulated by epigenetic factors, but disruptions in these mechanisms may lead to aberrant blood cell production. Acute myeloid leukemia (AML) is a malignant disorder characterized by the clonal proliferation of immature myeloid precursors in the bone marrow, at the expense of the production of healthy blood cells. In the last years, it has become increasingly clear that epigenetic dysregulation is a major contributor to the pathogenesis of AML: most patients carry mutations in epigenetic modulators, and epigenetic marks such as methylation can also identify biologically distinct subtypes. Furthermore, changes (genetic or epigenetic) in regulatory elements have been identified as drivers of altered gene expression.

The work presented in this thesis draws from molecular biology and bioinformatics alike to shed light on the role of transcription factors in healthy hematopoiesis, explore the mechanisms of enhancer hijacking in leukemia and identify novel epigenetic events underlying leukemogenesis. Knowledge of these epigenetic alterations and their molecular underpinnings opens the door to the development of targeted therapies that could selectively reverse the leukemogenic process.
Original languageEnglish
Awarding Institution
  • Erasmus University Rotterdam
  • Delwel, Ruud, Supervisor
  • Wouters, Bas, Co-supervisor
Award date19 Jan 2023
Place of PublicationRotterdam
Print ISBNs978-94-6361-791-8
Publication statusPublished - 19 Jan 2023


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