The role of epigenetic aberrations for leukemia biology and treatment response

With this application, we lay out our strategy to define how the epigenetic machinery is dysregulated in acute myeloid leukemia (AML), how it drives leukemia transformation and how it plays a role in the heterogenous treatment response.

Based on our previous research, we will further uncover previously unexplored areas in AML, with focus on the 3D organization of the chromatin and the role of long non-coding RNA.

We use genome-wide cutting-edge sequencing technologies, including single cell analyses, to define leukemia specific epigenetic changes and then use gene editing techniques to individually validate molecular features that are most likely to be important for AML transformation and treatment.

To improve understanding of biology and to provide novel tools for precision medicine, we use our own large AML biobanks to create extensive layers of data, analyzing the genome, transcriptome, epigenome, proteome and the drug sensitivity by cutting-edge techniques.

Analyses of the epigenome include ChIP-seq for chromatin states, ATAC-seq to identify transcribed parts of the genome and HiC to define intergenomic contacts. Data will be intregrated on a multiomic level.

To integrate the different data sets, we will use novel bioinformatic tools and artificial intelligence in collaboration with groups at Karolinska, KTH and RIKEN institute.

We will further develop and validate epigenetic markers as tools for precision medicine in a clinical trial with epigenetic treatment.