Frequent mutations in the GATA-1 gene in the transient myeloproliferative disorder of Down syndrome

Gang Xu, Masumi Nagano, Rika Kanezaki, Tsutomu Toki, Yasuhide Hayashi, Takeshi Taketani, Tomohiko Taki, Tetsuo Mitui, Kenichi Koike, Koji Kato, Masue Imaizumi, Isao Sekine, Yasuhiko Ikeda, Ryoji Hanada, Masahiro Sako, Kazuko Kudo, Seiji Kojima, Osamu Ohneda, Masayuki Yamamoto, Etsuro Ito

Research output: Contribution to journalArticlepeer-review

189 Citations (Scopus)


Transient myeloproliferative disorder (TMD) is a leukemoid reaction occurring occasionally in Down syndrome newborn infants. Acute megakaryocytic leukemia (AMKL) develops in approximately 20% to 30% of the cases with TMD. Recently, acquired mutations in the N-terminal activation domain of the GATA-1 gene, encoding the erythroid/megakaryocytic transcription factor GATA-1, have been reported in Down syndrome-related AMKL (DS-AMKL). To understand the multistep leukemogenesis in Down syndrome, GATA-1 mutations were investigated in patients with TMD. We show here that mutations in the GATA-1 gene were detected in 21 of 22 cases with TMD. Most of the mutations in TMD were located in the regions including exon 2 and were essentially identical to those observed in DS-AMKL. In the DS-AMKL cell line, MGS, which itself expresses only a truncated mutant of GATA-1, expression of full-length GATA-1 induced the differentiation toward the erythroid lineage. However, expression of the short form of GATA-1 did not induce erythroid differentiation. These results indicate that expression of GATA-1 with a defective N-terminal activation domain contributes to the expansion of TMD blast cells and that other genetic changes contribute to the development of AMKL in Down syndrome.

Original languageEnglish
Pages (from-to)2960-2968
Number of pages9
Issue number8
Publication statusPublished - 15-10-2003

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology


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