The Diamond Blackfan Anemia Foundation is proud to support the research of Dr. Shai Izraeli, Professor in the Department of Human Molecular Genetics and Biochemistry at Tel Aviv University and the Head of the Childhood Leukemia Research Institute within the Department of Pediatric Hematology/Oncology and the Cancer Research Center at Sheba Medical Center, Israel. The DBAF provided a $32,000 grant for Dr. Izraeli’s project entitled, A mouse model to study the role of GATA2 in anemia caused by GATA1s mutation.
Dr. Izraeli stated,
“Testing our hypothesis could not be done without the DBA Foundation’s funding. Given that I have been, until now, primarily a childhood leukemia researcher outside the bone marrow failure field and given the preliminary high risk hypothesis, no competitive grant would have funded this project. DBAF has given us the essential seed money to test our hypothesis. As a physician scientist I can testify that the patients and families give us the motivation to do this research.”
Inherited mutations in GATA1 leading to the formation of a shorter protein, called GATA1s, were recently discovered in several families with Diamond Blackfan Anemia. Dr. Izraeli has been interested in GATA1s since the same mutation appears in leukemias in patients with Down syndrome. While attempting to create a mouse model of these leukemias, Dr. Yehudit Birger, a senior investigator in Dr Izraeli’s laboratory, discovered that mice carrying the GATA1s mutations had fetal anemia. Detailed gene expression analysis revealed high expression of GATA2, another GATA factor. GATA2 and GATA1 have opposing activities on erythroid differentiation; GATA2 blocks, while GATA1 promotes, erythroid differentiation. Dr. Izraeli and Dr. Birger hypothesize that the high ratio of GATA2/GATA1s is at least partially responsible for the anemia observed in mice and humans with GATA1s mutation.
To test this hypothesis, they will conduct a genetic experiment lowering the dose of GATA2 in GATA1s mice. If successful, this experiment will lead to a search for GATA2 “druggable” targets whose modification may at least partially ameliorate the anemia in DBA patients with GATA1s mutations. Furthermore, the recent findings published by Dr. Vijay Sankaran and colleagues that suggest a deficiency in GATA1 underlies the broader class of DBA patients with ribosomal gene mutations, expands the potential relevance of Dr Izraeli’s proposed research.