PROJECT SUMMARY

GATA2 deficiency is a rare, inherited genetic syndrome found in children that arises from mutations in GATA2, which is a gene that is critical for proper blood development. These mutations result in a non-functional protein, which can lead to improper immunity and myelodysplastic syndrome (MDS). MDS is a disorder in which the bone marrow does not produce enough healthy blood cells and can often progress to acute leukemia. Unfortunately, 75% of patients with GATA2 deficiency develop blood disorders, including MDS, by early adulthood. To study this disease, I created a mouse model with a common GATA2 deficiency mutation, Gata2R396Q. These mice express a mutated form of GATA2 in every cell of their body, including blood cells. I also created a line of human cells expressing GATA2R396Q that can be used to model disease in the human setting. I use my mouse and human models to 1.) Determine the effects of GATA2 deficiency on normal blood development and 2.) Explore how GATA2 deficiency leads to MDS and acute leukemia. To do this, I am tracking the complexity of the blood system in Gata2R396Q mice and pairing other mutations found in GATA2 deficiency-related leukemia with my mouse and human models to identify regulators of disease progression. These studies provide new insights into the biology of GATA2 deficiency and will facilitate development of novel therapies to prevent or treat related blood disorders.