Grants - Translational Grants - Massachusetts - 2017

Timothy Graubert, M.D.

2017 V Foundation Wine Celebration Vintner Grant in honor of David and Kary Duncan

Myelodysplastic Syndromes (MDS) and Acute Myeloid Leukemia (AML) are blood cancers diagnosed in approximately 25,000 and 19,000 individuals each year in the US, respectively. Despite an enormous global effort, the treatments and outcomes for patients with MDS and AML have not improved significantly over the past 4 decades. The purpose of this study is to evaluate a new idea for MDS/AML therapy to see if there is sufficient promise to launch a clinical trial for patients at our center. 
 
By studying the genomes (the DNA blueprint in all cells) of patients with MDS/AML, the scientists involved in this proposal identified mutations (“mistakes”) in a structure called the spliceosome. These spliceosome mutations are very common in patients with MDS/AML. We recently found that the spliceosome-mutant cells are more readily killed in the laboratory by two drugs that are currently being tested in clinical trials for other cancers. 
 
In this project, we will test these two drugs alone and in combination using systems that we have developed in the laboratory. We will determine how, at the molecular level, these drugs kill the spliceosome-mutant cells and how they may become resistant to these treatments. Finally, we will develop tests to monitor the effects of these drugs when given to patients with MDS/AML. Since these drugs are already in clinical development for other indications, we expect that our work will rapidly help lay the foundation for clinical trials to see if these drugs offer new hope for patients with MDS and AML.