Mutational and transcriptomic landscapes in hematopoietic cells of Fanconi anemia patients

Fanconi anemia (FA) is a rare genetic disease caused by deficient DNA damage repair. Patients are at risk to develop bone marrow failure (BMF) and secondary myelodysplastic syndrome (MDS) and MDS-related acute myeloid leukemia (MDR-AML). In this project, we aim at understanding the mechanisms of hematopoietic failure and identifying driver mutations and dysregulated pathways involved in progression to MDS/AML. For this, we collected bone marrow samples from FA patients suffering from the different disease stages (i.e. BMF, low-grade MDS, advanced MDS and AML) and subjected them to WES and RNAseq. Preliminary transcriptome data revealed downregulation of DNA repair pathways and upregulation of pro-apoptotic genes in BMF samples. During disease progression towards MDS/AML, mutations in oncogenes and tumor suppressors accumulated. Our work will contribute to a greater understanding of the role of mutations and their deregulated gene expression in the advancement of FA-associated MDR-AML.