From CoREST to Cancer: Integrative Molecular Studies on Megakaryopoiesis and Retroviral Activity in AML

Abstract

Protein complexes are essential for cellular function, and while their components may be shared across cells, their behaviour varies in cells with different functions. Consequently, drugs targeting these proteins can have cell type–specific effects. This thesis investigates how inhibition of LSD1, part of a protein complex called CoREST, and mutations in its complex partner GFI1B impair the development and function of platelet-producing blood cells. LSD1 inhibition also activates ancient viral elements embedded in the DNA of blood cells, which are normally silent but may modulate responses to therapies for hematologic diseases such as blood cancer. A comprehensive understanding of these elements requires mapping their presence across different types of blood cancers. This thesis provides such a map by analysing ancient virus activity in approximately 800 patients with various blood cancer types, offering insight into how these ancient viral sequences might influence disease mechanisms and treatment outcomes.