The role of GATA2 in normal and malignant hematopoiesis

Emma de Pater studied Biology at the University of Leiden and graduated Sept 30^th 2005. June 3^rd 2010 she obtained her PhD from Utrecht University after completing her thesis on the growth of the zebrafish heart at the Hubrecht Institute in the group of Prof. Jeroen Bakkers. She started her postdoctoral work in the lab of Prof Elaine Dzierzak at Erasmus MC and investigated the role of the transcription factor Gata2 in the generation of hematopoietic stem cells (HSCs) in the mouse embryo. Here she discovered that GATA2 is required for HSC generation and maintenance at several stages during ontogeny. In 2015 she started her research group, combined with management of the cancer genome editing center, at the department of Hematology investigating the role of GATA2 in leukemia predisposition syndromes. Her group uses mouse-, zebrafish- and cell models to study the effects of GATA2 mutation on normal and malignant hematopoiesis. In 2017 she became assistant professor and since 2020 she combines management of her research group with management of the transplantation laboratory of the department of hematology. The transplantation laboratory is responsible for the processing of stem cell- and lymphocyte products with which over 300 patients are treated annually.

Our research

The de Pater lab studies the role of the transcription factor GATA2 in acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS).

The transcription factor GATA2 is recurrently mutated in AML. Furthermore, the most common germline defect in childhood MDS/AML is a mutation in GATA2. The mutational spectrum of GATA2 in these patients is very diverse, as are the phenotypes of the patients. Some patients have severe hematological deficiencies, while others only have a predisposition for MDS/AML. The reason for this is unknown. These patients have innate mutations in GATA2, which means that these mutations are also present during embryonic development of the hematopoietic system. Innate mutations in Gata2 in mouse and zebrafish result in a severe reduction in the number of HSCs that are generated in the embryo. A novel zebrafish model for GATA2 haploinsufficiency mimics patient characteristics like monocytopenia and dysplasia. The de Pater group is currently investigating the mechanism of malignant transformation in this model and the embryonic role of GATA2 to the contribution of leukemia predisposition. Furthermore, the types of mutations found in de novo AML and in patients with a germline predisposition for MDS/AML are different and how these mutations result in leukemogenesis and deregulate transcription are subject of active investigation.

Our team

Key publications