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

doi:10.1182/blood-2006-01-031781

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

Blood. 2007 May 1;109(9):4023-7. doi: 10.1182/blood-2006-01-031781. Epub 2007 Jan 23.

Authors

Norio Asou¹, Masatoshi Yanagida, Liqun Huang, Masayuki Yamamoto, Katsuya Shigesada, Hiroaki Mitsuya, Yoshiaki Ito, Motomi Osato

Affiliation

¹ Department of Hematology, Kumamoto University School of Medicine, 1-1-1 Honjo, Kumamoto 860-8556, Japan. [email protected]

PMID: 17244685
DOI: 10.1182/blood-2006-01-031781

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.

Publication types

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

MeSH terms

Animals
Cell Line
Cell Proliferation
Cell Transformation, Neoplastic / genetics
Cell Transformation, Neoplastic / metabolism*
Chromosomes, Human, Pair 21 / genetics
Chromosomes, Human, Pair 21 / metabolism
Chromosomes, Human, Pair 8 / genetics
Chromosomes, Human, Pair 8 / metabolism
Core Binding Factor Alpha 2 Subunit / biosynthesis*
Core Binding Factor Alpha 2 Subunit / genetics
DNA-Binding Proteins / biosynthesis*
DNA-Binding Proteins / genetics
GATA Transcription Factors / genetics
GATA Transcription Factors / metabolism*
Hematopoietic Stem Cells / metabolism
Humans
Leukemia, Myeloid, Acute / genetics
Leukemia, Myeloid, Acute / metabolism*
Mice
Oncogene Proteins, Fusion / biosynthesis*
Oncogene Proteins, Fusion / genetics
Repressor Proteins
Transcription Factors / biosynthesis*
Transcription Factors / genetics
Transcription, Genetic
Translocation, Genetic / genetics

Substances

Core Binding Factor Alpha 2 Subunit
DNA-Binding Proteins
GATA Transcription Factors
Oncogene Proteins, Fusion
RUNX1 protein, human
Repressor Proteins
TRPS1 protein, human
Transcription Factors