IWASAKI Masayuki
   Department   Research Institutes and Facilities, Research Institutes and Facilities
   Position   Assistant Professor
Article types Original article
Language English
Peer review Peer reviewed
Title Haploinsufficiency of Runx1/AML1 promotes myeloid features and leukaemogenesis in BXH2 mice.
Journal Formal name:British journal of haematology
Abbreviation:Br J Haematol
ISSN code:00071048/00071048
Domestic / ForeginForegin
Volume, Issue, Page 131(4),pp.495-507
Author and coauthor Yamashita Namiko, Osato Motomi, Huang Liqun, Yanagida Masatoshi, Kogan Scott C, Iwasaki Masayuki, Nakamura Takuro, Shigesada Katsuya, Asou Norio, Ito Yoshiaki
Publication date 2005/11
Summary Haploinsufficiency of RUNX1/AML1 is associated with familial platelet disorder with a predisposition to acute myeloid leukaemia (FPD/AML), but the causal relationship remains to be addressed experimentally. Mice heterozygous for the Runx1 null mutation, Runx1+/-, are considered to be genetically comparable with human FPD/AML patients but do not develop spontaneous leukaemia. To induce additional genetic alterations, retroviral insertional mutagenesis was employed with the use of BXH2 mice, which develop myeloid leukaemia because of the random integration of retrovirus present in the mouse. Heterozygous disruption of Runx1 in BXH2 mice resulted in a shortening of the latency period of leukaemia. In addition, BXH2-Runx1+/- mice exhibited more marked myeloid features than control mice. Moreover, the c-Kit gene, mutated in human RUNX leukaemias, was recurrently activated in BXH2-Runx1+/- mice, and a colony-forming assay revealed synergism between the Runx1+/- status and c-KIT overexpression. In conclusion, the BXH2-Runx1+/- system is a promising mouse model to investigate the mechanism of leukaemogenesis in FPD/AML.
DOI 10.1111/j.1365-2141.2005.05793.x
PMID 16281942