Using zebrafish to model the molecular origins of pediatric myeloid malignancies and acute myeloid leukemia

Myelodysplastic syndrome (MDS) is caused by the abnormal development of blood cells. Currently, the symptoms of MDS can be treated, but the disease itself remains incurable. About 50% of MDS-cases develop into deadly leukemia. The main reason that MDS is difficult to treat is that it is not a single disease, but consists of many subtypes with different symptoms and different underlying causes. To unravel MDS we need to exploit animal models, such as the zebrafish, that can realistically capture the complex disease and are accessible to experimental analysis in living animals. Zebrafish can develop blood cancers just like humans, and because zebrafish embryos develop outside the mother and are transparent, blood development can be observed in real time. Furthermore, the large number of offspring produced by zebrafish daily makes it feasible to test the contributions of combinations of defects to determine which ones give rise to MDS. The information acquired from these proposed studies will make it possible to design new specific therapies to treat the distinct subtypes of MDS. Moreover, the zebrafish models of MDS developed through these studies may themselves serve as the basis of future drug screens to identify new small molecules for treating MDS.