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

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

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Age of Onset
  • Child
  • Child, Preschool
  • Chromosome Aberrations
  • Chromosomes, Human, Pair 1 / genetics
  • Chromosomes, Human, Pair 7 / genetics
  • Chromosomes, Human, Pair 8 / genetics
  • Clinical Trials, Phase III as Topic
  • DNA Mutational Analysis
  • Deafness / genetics
  • Female
  • GATA2 Transcription Factor / deficiency*
  • GATA2 Transcription Factor / genetics
  • Genetic Predisposition to Disease
  • Germ-Line Mutation
  • Humans
  • Immunologic Deficiency Syndromes / genetics
  • Kaplan-Meier Estimate
  • Male
  • Myelodysplastic Syndromes / epidemiology
  • Myelodysplastic Syndromes / etiology
  • Myelodysplastic Syndromes / genetics*
  • Myelodysplastic Syndromes / pathology
  • Phenotype
  • Prevalence
  • Prognosis
  • Prospective Studies
  • Selection Bias
  • Young Adult

Substances

  • GATA2 Transcription Factor