Kate Amato Foundation Awarded Projects

Project Description:

GATA2 deficiency is a rare genetic condition that is usually diagnosed in younger patients who suffer multiple infections due to a weakened immune system. Many of these children or young adults have worsening blood cell counts which coincide with the development of blood cancers, such as acute leukemia. Although most cases of blood cancer in children do not have a clear cause, in GATA2 deficiency, it originates with a change in a single gene, GATA2. When blood cancer develops in patients with GATA2 deficiency, the subsequent genetic changes in the cancer cells are predictable: they tend to occur in the same places, and in the same genes. These specific changes appear to highlight a common path to developing blood cancer, with several genetic changes representing key steps needed for cancer to develop. However, despite knowing that these steps exist, we do not currently understand how they fit together, or why cancer arises so commonly in this condition.

Our goal is to study these genetic changes and understand how they interact to produce blood cancers. We hope to first target the two most common genetic changes, in the genes ASXL1 and SETBP1, and determine how they interact with GATA2 to cause cancer. We will then investigate a larger number of genetic changes, many of which have never been reported, to understand if there are other undiscovered pathways that can also lead to cancer in these young patients. To these ends, we hope that this work will help us better understand a rare disease that preferentially affects young patients, and help to set benchmarks to signal when and how cancer develops. By defining these steps, and how they function, we hope to help health care teams predict when a patient may develop blood cancer, and, in turn, intervene with specific and effective therapies.