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Blood. 2016 Mar 17;127(11):1387-97; quiz 1518. doi: 10.1182/blood-2015-09-669937. Epub 2015 Dec 23.

Prevalence, clinical characteristics, and prognosis of GATA2-related myelodysplastic syndromes in children and adolescents.

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Division of Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent Medicine, University of Freiburg, Freiburg, Germany; German Cancer Consortium, Freiburg, Germany, and German Cancer Research Center, Heidelberg, Germany;
Division of Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent Medicine, University of Freiburg, Freiburg, Germany;
Department of Pediatric Hematology and Oncology, Charles University and University Hospital Motol, Prague, Czech Republic;
Department of Pediatrics, Aarhus University Hospital Skejby, Aarhus, Denmark;
Department of Pediatric Oncology and Hematology, University of Bologna, Bologna, Italy;
St. Anna Children's Hospital and Children's Cancer Research Institute, Medical University of Vienna, Vienna, Austria;
Department of Hematology and Oncology, University Children's Hospital, Zurich, Switzerland;
Erasmus Medical Center, Rotterdam, and Dutch Childhood Oncology Group, The Hague, The Netherlands;
Department of Pediatric Hematology, Oncology, and BMT, Medical University of Wroclaw, Wroclaw, Poland;
Department of Pediatric Hematology-Oncology and Stem Cell Transplantation, Ghent University Hospital, Ghent, Belgium;
Department of Hematology and Oncology, Hospital Sant Joan de Déu, Barcelona, Spain;
Paediatric Oncology and Haematology, Our Lady's Children's Hospital Crumlin, Dublin, Ireland;
Department of Pediatrics, Leiden University Medical Center, Leiden, The Netherlands;
Pediatric Hematology-Oncology, Fondazione Istituti di ricovero e cura a carattere scientifico (IRCCS) Policlinico San Matteo, Pavia, Italy;
Pediatric Oncology, Queen Silvias Children's Hospital, Gothenburg, Sweden;
Pediatric Oncology, Charité-University Medicine Berlin, Berlin, Germany;
Pediatric Hematology and Oncology, Hannover Medical School, Hannover, Germany;
Department of Pediatric Hematology and Oncology, Dr.v.Hauner Children's Hospital, Ludwig-Maximilians-University, Munich, Germany;
Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH;
Institute of Pathology, University of Erlangen, Erlangen, Germany;
Institute of Human Genetics, Hannover Medical School, Hannover, Germany;
Department of Pediatric Hematology and Oncology, Bambino Gesù Children's Hospital, Rome, University of Pavia, Pavia, Italy; and.
Department of Pathology, Clinical Center, Böblingen, Germany.


Germline GATA2 mutations cause cellular deficiencies with high propensity for myeloid disease. We investigated 426 children and adolescents with primary myelodysplastic syndrome (MDS) and 82 cases with secondary MDS enrolled in 2 consecutive prospective studies of the European Working Group of MDS in Childhood (EWOG-MDS) conducted in Germany over a period of 15 years. Germline GATA2 mutations accounted for 15% of advanced and 7% of all primary MDS cases, but were absent in children with MDS secondary to therapy or acquired aplastic anemia. Mutation carriers were older at diagnosis and more likely to present with monosomy 7 and advanced disease compared with wild-type cases. For stratified analysis according to karyotype, 108 additional primary MDS patients registered with EWOG-MDS were studied. Overall, we identified 57 MDS patients with germline GATA2 mutations. GATA2 mutations were highly prevalent among patients with monosomy 7 (37%, all ages) reaching its peak in adolescence (72% of adolescents with monosomy 7). Unexpectedly, monocytosis was more frequent in GATA2-mutated patients. However, when adjusted for the selection bias from monosomy 7, mutational status had no effect on the hematologic phenotype. Finally, overall survival and outcome of hematopoietic stem cell transplantation (HSCT) were not influenced by mutational status. This study identifies GATA2 mutations as the most common germline defect predisposing to pediatric MDS with a very high prevalence in adolescents with monosomy 7. GATA2 mutations do not confer poor prognosis in childhood MDS. However, the high risk for progression to advanced disease must guide decision-making toward timely HSCT.

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