FLT3/ITD Mouse Model for Acute Myeloid Leukemia (AML)

Unmet Need: Constitutive activation of FMS-like tyrosine kinase 3 (FLT3) by internal tandem duplication (ITD) mutations is one of the most common molecular alterations known in acute myeloid leukemia (AML). To investigate the role FLT3/ITD mutations play in the development of leukemia, we generated a FLT3/ITD knock-in mouse model by inserting an ITD mutation into the juxtamembrane domain of murine Flt3 genomic DNA. The FLT3/ITD knock-in may serve as an ideal model for:
 
(1) studying in vivo the roles FLT3/ITD mutations play in the development and maintenance of leukemia;
(2) understanding the mechanisms of how other mutations cooperate with FLT3/ITD mutations to cause leukemia;
(3) screening new drugs targeting FLT3 mutations.
 
Value Proposition: Phenotypic analyses indicate that expression of the FLT3/ITD mutation alone is capable of conferring myeloproliferative disease. This mouse model closely simulates and reflects the events that occur when a normal mouse hematopoietic cell acquires an activating FLT3 mutation and hence provides a useful platform to study the roles of FLT3/ITD mutations in the development and maintenance of leukemia. It also provides a valuable tool for screening novel drugs targeting FLT3 mutations.

Data Availability: Mouse Model

Associated Publications: Blood. 2008 Apr 1;111(7):3849-58.

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