Miriam Erlacher, Germany

University Medical Center Freiburg Division of Pediatric Hematology and Oncology
Since 2018: Study Physician EWOG-MDS and EWOG-SAA 2016: Board certification in pediatric hematology and oncology 2013: Board certification in pediatric and adolescent medicine Since 2013: Clinician Scientist 2006: PhD (Innsbruck Medical University, Austria) 2003: MD (University of Innsbruck, Austria)

Presenter Of 1 Presentation

Parallel Session No Topic Needed

GATA2 IN MDS

Lecture Time
16:30 - 16:55
Room
Bozar
Date
20.09.2019, Friday
Session Time
16:30 - 18:10
Presentation Topic
No Topic Needed

Abstract

Abstract Body

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.

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