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Haploinsufficiency of Runx1/AML1 promotes myeloid features and leukaemogenesis in BXH2 mice
- Source :
- British journal of haematology. 131(4)
- Publication Year :
- 2005
-
Abstract
- 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.
- Subjects :
- medicine.medical_specialty
Myeloid
Platelet disorder
Genetic Vectors
Mutagenesis (molecular biology technique)
Mice, Inbred Strains
Biology
Polymerase Chain Reaction
Colony-Forming Units Assay
chemistry.chemical_compound
Mice
hemic and lymphatic diseases
Internal medicine
medicine
Animals
Humans
Point Mutation
Genetic Predisposition to Disease
Hematology
medicine.disease
Null allele
Neoplasm Proteins
Mice, Inbred C57BL
Leukemia
Disease Models, Animal
Mutagenesis, Insertional
Proto-Oncogene Proteins c-kit
medicine.anatomical_structure
Retroviridae
RUNX1
chemistry
Haplotypes
Leukemia, Myeloid
embryonic structures
Core Binding Factor Alpha 2 Subunit
Cancer research
Haploinsufficiency
Subjects
Details
- ISSN :
- 00071048
- Volume :
- 131
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- British journal of haematology
- Accession number :
- edsair.doi.dedup.....160abc67cdc2839860e2d9d6f28e3e31