RUNX1 and CBFB are among the most frequently mutated genes in human
leukemias. Genetic alterations such as
chromosomal translocations, copy number variations and point mutations have been widely reported to result in the malfunction of RUNX
transcription factors.
Leukemias arising from such alterations in RUNX family genes are collectively termed
core binding factor (CBF)
leukemias. Although adult CBF
leukemias generally are considered a favorable risk group as compared with other forms of
acute myeloid leukemia, the 5-year survival rate remains low. An improved understanding of the molecular mechanism for CBF
leukemia is imperative to uncover novel treatment options. Over the years, retroviral transduction-
transplantation assays and transgenic, knockin and knockout mouse models alone or in combination with mutagenesis have been used to study the roles of RUNX alterations in leukemogenesis. Although successful in inducing
leukemia, the existing assays and models possess many inherent limitations. A CBF
leukemia model which induces
leukemia with complete penetrance and short latency would be ideal as a platform for
drug discovery. Here, we summarize the currently available mouse models which have been utilized to study CBF
leukemias, discuss the advantages and limitations of individual experimental systems, and propose suggestions for improvements of mouse models.