Project information
A multiomics approach to better understand the impact of chromatin reorganization on leukemia progression

Chronic lymphocytic leukemia (CLL) is the most prevalent and still incurable form of adulthood leukemia in the Western world, affecting mature B lymphocytes. It has a highly heterogeneous clinical presentation when some patients experience slow disease progression while others face an aggressive course, which underscores the urgent need for research into the molecular mechanisms and genetic factors driving this variability. Although it is known that genetic alterations contribute to changes in molecular cellular processes, their exact consequences remain unclear in many instances. This challenge is particularly pronounced in patients with complex structural variants (cSVs) of their chromosomes that are associated with an aggressive disease course.
For all molecular processes happening in living cells, the structure of cellular chromatin is essential. Chromatin organization generally includes A/B compartments, topologically associated domains (TADs), and chromatin loops. Genetic alterations may cause chromatin reorganization, leading to aberrant gene expression. We hypothesize that chromatin reorganization is also an important determinant of gene expression regulation in CLL cells. We are particularly interested in studying the 3D chromatin structure in relation to cSVs and understanding how structural changes drive leukemia pathophysiology. To explore how these chromatin rearrangements affect gene regulation, we will combine our already-collected data from the Micro-C method (high-throughput chromatin conformation capture), whole-genome sequencing (WGS) and RNA sequencing (RNA-seq) to understand how the spatial changes in chromatin structure impact gene regulation.
Our multi-omics approach, allowing us to map chromatin architecture and gene expression simultaneously, promises to advance our understanding of the molecular underpinnings of CLL. Through this integrated analysis, we hope to uncover novel insights into CLL pathogenesis and identify potential therapeutic targets.