The core-binding factor leukemias: lessons learned from murine models.
The recent development of murine models of core-binding factor leukemias has provided important insights into the underlying molecular pathology of this common subtype of acute myeloid leukemia. Evidence from these models supports the idea that acute myeloid leukemia 1/core-binding factor beta-subunit (AML1/CBFbeta) has a critical role in the control of the self-renewal capacity of hematopoietic stem cells and their progeny. Moreover, the accumulated data demonstrate that the expression of translocation-encoded AML1 or CBFbeta fusion proteins are insufficient by themselves to induce a full leukemic phenotype. The models that have been developed should prove to be of value for defining the range of mutations that can cooperate with AML1/CBFbeta fusion proteins, and for assessing novel therapies targeted toward the pathways that are altered by the expression of these fusion proteins.
Downing
James R
JR
Department of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA. jim.downing@stjude.org
D000818:Animals; D050676:Core Binding Factor Alpha 2 Subunit; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D004195:Disease Models, Animal; D007938:Leukemia / Q000209:etiology / Q000235:genetics; D051379:Mice; D009154:Mutation; D011518:Proto-Oncogene Proteins; D050656:Transcription Factor AP-2; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D014158:Transcription, Genetic / Q000502:physiology*
D050676:Core Binding Factor Alpha 2 Subunit; D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; C493726:Runx1 protein, mouse; D050656:Transcription Factor AP-2; D014157:Transcription Factors