PROJECT SUMMARY

Acute Myeloid Leukemias (AML) and Myelodysplastic Syndromes (MDS) are a frequent and deadly cause of blood cancers in adults. While we do not fully understand how these cancers begin, individuals carrying inherited mutations in the DDX41 gene are more likely to develop MDS and AML as they age. Through this project, I seek to better understand how genetic mutations in DDX41 influence genes in blood-forming cells and promote the development of MDS/AML. I will first investigate how the DDX41 mutations observed in patients affect the activity and the regulation of other genes in human blood-forming cells. I will then use genetic tools to correct the gene pathways that are malfunctioning in mutated cells and restore their activity. The goal is to identify new treatments that could stop the harmful effects of DDX41 mutations and prevent blood cancers from developing. Many patients with DDX41 mutations who develop MDS or AML carry additional mutations in other genes. To understand how they speed up the development of blood cancers, I will compare the behavior of blood-forming cells carrying mutations in DDX41 and in another gene to cells carrying DDX41 mutations only. This approach will clarify how mutations work together in blood-forming cells to increase the risk of blood cancer. By studying how DDX41 mutations damage human blood-forming cells, I aim to find new ways to specifically target these harmful deregulations and treat blood cancers like MDS and AML.