Concurrent transcriptional deregulation of AML1/RUNX1 and GATA factors by the AML1-TRPS1 chimeric gene in t(8;21)(q24;q22) acute myeloid leukemia

Norio Asou, Masatoshi Yanagida, Liqun Huang, Masayuki Yamamoto, Katsuya Shigesada, Hiroaki Mitsuya, Yoshiaki Ito, Motomi Osato

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

The Runt domain transcription factor AML1/RUNX1 is essential for the generation of hematopoietic stem cells and is the most frequent target of chromosomal translocations associated with leukemia. Here, we present a new AML1 translocation found in a patient with acute myeloid leukemia M4 with t(8;21)(q24;q22) at the time of relapse. This translocation generated an in-frame chimeric gene consisting of the N-terminal portion of AML1, retaining the Runt domain, fused to the entire length of TRPS1 on the C-terminus. TRPS1 encodes a putative multitype zinc finger (ZF) protein containing 9 C2H2 type ZFs and 1 GATA type ZF. AML1-TRPS1 stimulated proliferation of hematopoietic colony-forming cells and repressed the transcriptional activity of AML1 and GATA-1 by 2 different mechanisms: competition at their cognate DNA-binding sites and physical sequestrations of AML1 and GATA-1, suggesting that simultaneous deregulation of AML1 and GATA factors constitutes a basis for leukemogenesis.

Original languageEnglish
Pages (from-to)4023-4027
Number of pages5
JournalBlood
Volume109
Issue number9
DOIs
Publication statusPublished - 2007 May 1
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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