TARGET-seq genotyped single-cell RNA sequencing of hematopoietic stem cells and megakaryocyte-erythroid progenitor cells from a dual SF3B1-mutant MDS-RS patient and 3 healthy donors

This translational research program aims at improving outcome for patients with myelodysplastic syndromes (MDS) by unravelling cellular and molecular mechanisms underlying disease features and response to treatment. Using a world-unique database of clinically annotated MDS patients who have undergone targeted DNA sequencing and RNA sequencing of CD34+ BM cells and has been complemented with comprehensive information regarding transfusion patterns and response to treatment we aim to develop novel predictive models for estimation of age-related survival loss, risk for progression, and optimal management and treatment. By using advanced culture models for human hemopoietic stem cell (HSC) biology and erythroid maturation in combination with single cell sequencing we will explore SF3B1 mutated MDS with ring sideroblasts with the aim to understand the clonal advantage of mutated over normal HSC and explore new molecular routes to prevent ineffective erythropoiesis and chronic transfusion dependency. Finally, we aim to implement and further improve recently developed methods for personalized minimal residual disease monitoring in a prospective clinical trial and thereby improve the cure rate after allogeneic stem cell transplantation in high-risk MDS. The long-term goal is to implement precision medicine in MDS in order to be able to predict and implement optimal management for each patient.