PROJECT SUMMARY

Our group is trying to better understand a blood disorder called MDS (myelodysplastic syndromes). MDS is commonly caused by mutations, or changes in a person’s DNA, that impair the ability of blood stem cells to make the different types of cells within blood that we need for critical functions, such as fighting infections and stopping bleeding. The mutations can vary depending on a person’s age, with some of these gene mutations being more common in children and young adults than older adults.

Recently, we identified mutations in the gene UBTF (upstream binding transcription factor).  Due to the complex nature of these mutations, which are called tandem duplications, many previous studies have underestimated how common these mutations are in MDS.  Recent work has shown these mutations to be common in teens and young adults with MDS. Individuals with this mutation can also develop acute myeloid leukemia (AML), and these patients have a dismal outcome.  Our previous studies have shown that UBTF-TD is the initial and driving mutation of disease. To study this mutation, we have made human models and a new mouse model that carries a UBTF-TD mutation in blood cells. These mice develop altered blood development, just like humans with the same DNA mutation. Our goal is to learn how this mutation functions in blood cells and ultimately leads to MDS. We are using advanced tools to look at how genes are turned on or off in cells and what happens when the UBTF-TD protein is removed.