Genetic Dissection of Cytogenetically Normal AML

Background

Acute myeloid leukemia (AML) is a genetically complex group of cancers. AML pediatric patients can be divided into those with chromosomal translocations and patients that are cytogenetically normal (CN-AML). Human-in-animal and mouse models of AML have been developed to validate fusion oncoproteins (e.g. AML-ETO and MLL-AF9) as direct effectors of leukemia initiation, disease pathogenesis, and therapeutic response.

In contrast, modeling the somatic mutations found in human CN-AML has been less successful. Because CN-AML represents nearly 50% of human AML cases, there is a dire need for validated genetically-defined animal models to address pressing biological and therapeutic questions in CN-AML. 

Project Goal

We have generated a rapid, spontaneous and accurate mouse model of human CN-AML, and we plan to use genome editing to identify genes that drive the leukemia forward. These genes should identify novel opportunities for clinical intervention.