Single-cell analysis of leukemic stem cells to predict therapy insensitivity and relapse

I have established an advanced infrastructure for single-cell genomics in Lund, implemented protocols beyond state-of-the art, and developed novel computational tools for optimized analysis of single-cell molecular data. I will use these methods to1. Delineate the heterogeneity of the human hematopoietic stem cell (HSCs) population and identify novel HSC markers.2.

With access to unique patient material from two clinical trials, I will dissect the leukemic stem cell (LSC) population from CML patients at diagnosis, molecular remission, and early stages of relapse.3.

Having highly purified populations at hand I will perform chromatin analysis to reveal the mechanism of TKI-insensitivity and to identify novel therapeutic targets for CML as well as regulators of human HSCs. 4.

Using a mitochondrial DNA based single-cell multiomics approach I will track clonal evolution in leukemia patients on therapyLSCs are a critical priority as targets for therapy and believed to reside in the HSC population.

However, this population is heterogeneous and the immunophenotype of residual, therapy-resistant LSCs remains unclear, hampering our understanding of the unique features of LSCs.

Here our technical expertise in single-cell genomics is combined with clinical trials in a three-year proposal to define and prospectively isolate TKI insensitive LSCs with relevance for therapy response as well to identify prognostic biomarkers for treatment-free remission.