Mutations in GATA1 in both transient myeloproliferative disorder and acute megakaryoblastic leukemia of Down syndrome

Blood Cells Mol Dis. Nov-Dec 2003;31(3):351-6. doi: 10.1016/j.bcmd.2003.08.001.


Mutations in transcription factors often contribute to human leukemias by providing a block to normal differentiation. To determine whether mutations in the hematopoietic transcription factor GATA1 are associated with leukemia, we assayed for alterations in the GATA1 gene in bone marrow samples from patients with various subtypes of acute leukemia. Here we summarize our findings that GATA1 is mutated in the leukemic blasts of patients with Down syndrome acute megakaryoblastic leukemia (DS-AMKL). We did not find mutations in GATA1 in leukemic cells of DS patients with other types of acute leukemia, or in other patients with AMKL who did not have DS. Furthermore, we did not detect GATA1 mutations in DNAs from over 75 other patients with acute leukemia or from 21 healthy individuals. Since the GATA1 mutations were restricted to DS-AMKL, we also investigated whether GATA1 was altered in the "preleukemia" of DS, transient myeloproliferative disorder (TMD). TMD is a common myeloid disorder that affects 10% of DS newborns and evolves to AMKL in nearly 30% patients. We detected GATA1 mutations in TMD blasts from every infant examined. Together, these results demonstrate that GATA1 is likely to play a critical role in the etiology of TMD and DS-AMKL, and that mutagenesis of GATA1 represents a very early event in DS myeloid leukemogenesis. We hypothesize that disruption of normal GATA-1 function is an essential step in the initiation of megakaryoblastic leukemia in DS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bone Marrow / pathology
  • DNA Mutational Analysis
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism
  • Disease Progression
  • Down Syndrome / complications
  • Down Syndrome / genetics*
  • Erythroid-Specific DNA-Binding Factors
  • GATA1 Transcription Factor
  • Humans
  • Leukemia, Megakaryoblastic, Acute / complications
  • Leukemia, Megakaryoblastic, Acute / genetics*
  • Mutation / genetics*
  • Myeloproliferative Disorders / complications
  • Myeloproliferative Disorders / genetics*
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism


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