Funded by: MDS Foundation, Inc.
Grant Year: 2023-2025
Research Center: Washington University in St. Louis
Research Title: Genetic Determinates of Clonal Hematopoiesis and Progression to Myelodysplastic Syndrome
Summary: MDS is known to have germline genetic underpinnings but only a small portion of its genetic inheritance is currently explained. Clonal hematopoiesis is thought to be the origin of many cases of MDS yet only a small proportion of individuals with CH will go on to develop MDS. In preliminary studies, we found that pathogenic germline variants (PGVs) confer high risks of CH and that PGVs and CH interact to predict risk of MDS. Here, we propose to first, validate our preliminary findings and second, to characterize the mechanisms through which germline mutations influence the acquisition and evolution of CH to MDS.
Funded by: MDS Foundation, Inc.
Grant Year: 2023-2025
Research Center: Karolinska Institutet
Research Title: Exploring hematopoietic stem and progenitor cell biology towards new targeted therapies for SF3B1mt myelodysplastic syndromes with ring sideroblasts
Summary: This project will investigate the molecular biology of primary hematopoietic stem and progenitor cells (HSPC) with mutations in the spliceosome component SF3B1. The overarching goal is to identify novel treatment options in SF3B1mt MDS with ring sideroblasts, where median overall survival is ~5 years. We will explore HSPC biology through state-of-the-art multiomics approaches and validate our discoveries using disease models to ultimately pave the way for targeted treatment of SF3B1mt MDS-RS.