Patients with familial mutations in GATA2 develop a bone marrow failure syndrome with varying cytopenias in different hematopoietic lineages and an 80% chance to develop leukemia during their lifetime. Although GATA2 haploinsufficient mouse models existed, none described any of these pathologic phenotypes. My group set out to generate and further investigate animal models for GATA2 haploinsufficiency syndromes to understand the molecular mechanism behind the disease characteristics. Using these novel models we have shown that homozygous deletion of Gata2b in zebrafish resulted in neutropenia and increased, but incomplete, B cell differentiation. This mimics the cytopenias seen in a portion of the human patients. Importantly, these lineage changes were resulting from transcriptional changes originating in the HSC compartment. Another important finding was that the heterozygous deletion of Gata2b in zebrafish resulted in myelodysplasia. Myelodysplasia is the primary form of malignant transformation in human patients with GATA2 haploinsufficiency. Furthermore, we could show that after aging and transplantation, the mouse Gata2 haploinsufficient model developed monocytopenia, neutropenia and B cell lymphopenia followed by HSC exhaustion. These are key aspects of the bone marrow failure syndrome in human patients. The distinction between the phenotype of homozygous and heterozygous mutant Gata2b suggests that GATA2 dosage is vital for different hematopoietic functionalities explaining the great variety in disease phenotypes in GATA2 haploinsufficiency patients. Our main interest is to understand what drives the phenotypic heterogeneity between patients, why these patients develop leukemia and what the molecular mechanism is behind GATA2 deficiency syndromes.