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Cre recombinase expression cooperates with homozygous FLT3 internal tandem duplication knockin mouse model to induce acute myeloid leukemia

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Item Type:Article
Title:Cre recombinase expression cooperates with homozygous FLT3 internal tandem duplication knockin mouse model to induce acute myeloid leukemia
Creators Name:Straube, J. and Eifert, T. and Vu, T. and Janardhanan, Y. and Haldar, R. and von Eyss, B. and Cooper, L. and Bruedigam, C. and Ling, V.Y. and Cooper, E. and Patch, A.M. and Bullinger, L. and Schnoeder, T.M. and Bywater, M. and Heidel, F.H. and Lane, S.W.
Abstract:Murine models offer a valuable tool to recapitulate genetically defined subtypes of AML, and to assess the potential of compound mutations and clonal evolution during disease progression. This is of particular importance for difficult to treat leukemias such as FLT3 internal tandem duplication (ITD) positive AML. While conditional gene targeting by Cre recombinase is a powerful technology that has revolutionized biomedical research, consequences of Cre expression such as lack of fidelity, toxicity or off-target effects need to be taken into consideration. We report on a transgenic murine model of FLT3-ITD induced disease, where Cre recombinase expression alone, and in the absence of a conditional allele, gives rise to an aggressive leukemia phenotype. Here, expression of various Cre recombinases leads to polyclonal expansion of FLT3(ITD/ITD) progenitor cells, induction of a differentiation block and activation of Myc-dependent gene expression programs. Our report is intended to alert the scientific community of potential risks associated with using this specific mouse model and of unexpected effects of Cre expression when investigating cooperative oncogenic mutations in murine models of cancer.
Keywords:Animal Disease Models, Gene Duplication, Acute Myeloid Leukemia, Mutation, fms-Like Tyrosine Kinase 3, Transgenic Mice, Animals, Mice
Source:Leukemia
ISSN:0887-6924
Publisher:Nature Publishing Group
Volume:37
Number:4
Page Range:741-750
Date:April 2023
Official Publication:https://doi.org/10.1038/s41375-023-01832-0
PubMed:View item in PubMed

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