Miriam Erlacher, GermanyUniversity Medical Center Freiburg Division of Pediatric Hematology and Oncology
Presenter Of 1 Presentation
GATA2 IN MDS
Myelodysplastic syndrome (MDS) is characterized by pancytopenia due to ineffective hematopoiesis and a propensity for acute myeloid leukemia (AML). MDS is frequent in old age, but rarely occurs in children and adolescents. Genetic work-up revealed that the mutational landscape differs between adults and young people, and that the latter frequently develop MDS on the background of a genetic syndrome.
In 2011, three syndromes were described to be caused by germline GATA2 mutations, indicating a broad phenotypic spectrum of the GATA2 deficiency syndrome. Immunodeficiency due to variable cytopenias is the major feature of affected individuals with B lymphocytopenia being the most consistent finding. The risk to develop MDS/AML was already noted in the index families, but unexpectedly, germline GATA2 mutations were also detected in pediatric MDS patients lacking a family history or syndromic features. The European Working Group of MDS in Childhood (EWOG-MDS) reports germline GATA2 mutations in 7% of all pediatric MDS with a higher prevalence in MDS with excess blasts (15%). There is a significant association with monosomy 7, der(1;7) and trisomy 8. Hematopoietic stem cell transplantation is curative resulting in outcomes similar to that observed for GATA2 wildtype MDS patients. Although most mutation carriers will eventually develop MDS/AML, disease manifestation may strongly be influenced by additional factors such as secondary events. We developed a mouse model reminiscent of the human disease with pancytopenia, bone marrow hypocellularity and leukemia occurring in a subset of animals. This model will help to identify mechanistic links between GATA2 haploinsufficiency and cooperating factors.