Duy Nguyen: Exploring the Role of DDX41 in MDS and AML in a Zebrafish Model

<p dir="ltr">Co-occurrence of somatic and germline mutations in the DEAD-box RNA helicase-1 (DDX41) are associated with familial myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML), and are found in about 5% of patients. We aim to understand the mechanisms behind the acquisition of second-hit somatic DDX41 mutations and co-operating mutations in other genes, in the context of MDS/AML development. For this, we have established a zebrafish line with a heterozygous ddx41 LOF mutation and a leukemogenic CALM-AF10 fusion (CALM-AF10+/ddx41HET). Next, we’ll compare the CALM-AF10+/ddx41HET model with CALM-AF10-/ddx41HET and CALM-AF10+/ddx41WT to observe the differences in MDS/AML development speed. We’ll also compare gene expression profile and forward/side scatter profile, respectively using RNA sequencing and flow cytometry. Next, we plan to treat the CALM/AF10+/ddx41HET model with cGAS-STING pathway suppression drugs to examine potential impeding effects on MDS/AML development.</p>