Submitted January 30, 2006
Accepted December 2, 2006
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, and Motomi Osato
Dept of Hematology, Kumamoto University School of Medicine, Kumamoto, Japan
Institute of Molecular and Cell Biology, Singapore
Institute of Basic Medical Science, and Center for Tsukuba Advanced Research Alliance, University of Tsukuba, Ibaraki, Japan
Institute for Virus Research, Kyoto University, Kyoto, Japan
Oncology Research Institute, National University of Singapore, Singapore
* Corresponding author; email: ktcnasou{at}gpo.kumamoto-u.ac.jp.
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 case of 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 nine C2H2 type ZFs and one GATA type ZF. AML1-TRPS1 stimulated proliferation of hematopoietic colony forming cells and repressed the transcriptional activity of AML1 and GATA-1 in two different mechanisms: competition at their cognate DNA binding sites and physical sequestrations of AML1 and GATA-, suggesting that simultaneous deregulation of AML1 and GATA factors constitutes a basis for leukemogenesis.
