Increased dosage of Runx1/AML1 acts as a positive modulator of myeloid leukemogenesis in BXH2 mice

Masatoshi Yanagida, Motomi Osato, Namiko Yamashita, Huang Liqun, Bindya Jacob, Feng Wu, Xinmin Cao, Takuro Nakamura, Tomomasa Yokomizo, Satoru Takahashi, Masayuki Yamamoto, Katsuya Shigesada, Yoshiaki Ito

Research output: Contribution to journalArticlepeer-review

33 Citations (Scopus)

Abstract

The RUNX1/AML1 gene on chromosome 21 is most frequently inactivated in human leukemias. In addition, an increased dose of RUNX1 is suggested as a basis for several kinds of leukemias. Amplifications of chromosome 21 or the RUNX1 gene are shown to be associated with leukemias with lymphoid lineage, whereas its involvement in myeloid lineage remains unclear. In this study, we generated GATA-1 promoter-driven Runx1 transgenic (Tg) mice, which showed a transient mild increase of megakaryocyte marker-positive myeloid cells but no spontaneous leukemia. These mice were then crossed with BXH2 mice, which have a replication-competent retrovirus in the mouse and develop myeloid leukemia due to insertional mutagenesis by random integration of the virus. Overexpressed Runx1 transgene in BXH2 mice resulted in shortening of the latency of leukemia with increased frequency of megakaryoblastic leukemia, suggesting that increased Runx1 dosage is leukemogenic in myeloid lineage. Identifications of retroviral integration sites revealed the genetic alterations that may cooperate with Runx1 overdose in myeloid leukemogenesis. This mouse model may be useful for analysing the pathogenesis of myeloid leukemias with RUNX1 overdose, especially to examine whether an extra-copy of RUNX1 by trisomy 21 is causally related to Down's syndrome-related acute megakaryoblastic leukemia (DS-AMKL).

Original languageEnglish
Pages (from-to)4477-4485
Number of pages9
JournalOncogene
Volume24
Issue number28
DOIs
Publication statusPublished - 2005 Jun 30
Externally publishedYes

Keywords

  • CBF
  • Down syndrome
  • GATA-1
  • Megakaryoblastic leukemia
  • Runx

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Fingerprint Dive into the research topics of 'Increased dosage of Runx1/AML1 acts as a positive modulator of myeloid leukemogenesis in BXH2 mice'. Together they form a unique fingerprint.

Cite this