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

Marcin W. Wlodarski, Shinsuke Hirabayashi, Victor Pastor, Jan Starý, Henrik Hasle, Riccardo Masetti, Michael Dworzak, Markus Schmugge, Marry Van Den Heuvel-Eibrink, Marek Ussowicz, Barbara De Moerloose, Albert Catala, Owen P. Smith, Petr Sedlacek, Arjan C. Lankester, Marco Zecca, Victoria Bordon, Susanne Matthes-Martin, Jonas Abrahamsson, Jörn Sven KühlKarl Walter Sykora, Michael H. Albert, Bartlomiej Przychodzien, Jaroslaw P. Maciejewski, Stephan Schwarz, Gudrun Göhring, Brigitte Schlegelberger, Annámaria Cseh, Peter Noellke, Ayami Yoshimi, Franco Locatelli, Irith Baumann, Brigitte Strahm, Charlotte M. Niemeyer

Research output: Contribution to journalArticlepeer-review

297 Citations (Scopus)

Abstract

GermlineGATA2 mutations cause cellular deficiencieswith 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 (EWOGMDS) 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 GATA2mutations. GATA2 mutations were highly prevalent among patients with monosomy 7 (37%, all ages) reaching its peak in adolescence (72%of adolescents withmonosomy 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 diseasemust guide decision-making toward timely HSCT.

Original languageEnglish
Pages (from-to)1387-1397
Number of pages11
JournalBlood
Volume127
Issue number11
DOIs
Publication statusPublished - 17 Mar 2016
Externally publishedYes

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