Tetrasomy 21 transient leukemia with a GATA1 mutation in a phenotypically normal trisomy 21 mosaic infant: case report and review of the literature

Pediatr Blood Cancer. 2005 Jan;44(1):85-91. doi: 10.1002/pbc.20161.


Infants with constitutional trisomy 21 are at increased risk of developing transient and acute megakaryoblastic leukemia (AMKL). Mutations in GATA1 have been identified in trisomy 21 patients with AMKL, and this lesion is thought to be an initial event by virtue of its presence during transient leukemia. Transient leukemia is also observed in phenotypically normal infants albeit much less commonly so. Almost all these infants are mosaic for trisomy 21, and the clinical course of transient leukemia recapitulates that observed in constitutional trisomy 21. We report a phenotypically normal infant with tetrasomy 21 transient leukemia, GATA1 mutation within exon 2, and trisomy 21 mosaicism restricted to the hematopoietic tissue. Two years after diagnosis, low levels of trisomy 21 persisted in the peripheral blood, which resolved 2.5 years after diagnosis. The GATA1 mutation was not detected at last follow-up. The literature review identified 32 phenotypically normal infants with transient leukemia. Ninety-one percent (29 of 32) were observed and three received chemotherapy at diagnosis of transient leukemia. Nineteen percent (6 of 32) developed acute leukemia, and four continued in remission (two died). Transient leukemia in trisomy 21 mosaicism recapitulates the condition observed in constitutional trisomy 21 at the biological and clinical levels. Infants should be followed for the development of acute leukemia.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Aneuploidy
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • DNA-Binding Proteins / genetics*
  • Down Syndrome / genetics*
  • Erythroid-Specific DNA-Binding Factors
  • Female
  • GATA1 Transcription Factor
  • Humans
  • Infant, Newborn
  • Leukemia, Megakaryoblastic, Acute / etiology
  • Leukemia, Megakaryoblastic, Acute / genetics*
  • Male
  • Mutation
  • Phenotype
  • Prognosis
  • Risk Factors
  • Transcription Factors / genetics*


  • DNA-Binding Proteins
  • Erythroid-Specific DNA-Binding Factors
  • GATA1 Transcription Factor
  • GATA1 protein, human
  • Transcription Factors