小鼠模型是重要的工具，可以复制遗传定义的AML亚型，并评估疾病进展过程中复合基因突变和克隆演化的潜力，对于难治性白血病如FLT3内串联复制（ITD）阳性AML尤其重要。虽然Cre重组酶的条件基因靶向是一种革命性的、强大的技术，但Cre表达的后果如缺乏保真性、毒性或离靶效应需要考虑。我们报道了一种FLT3-ITD诱导疾病的转基因小鼠模型，在这种模型中，Cre重组酶表达单独存在，并且在没有条件等位基因的情况下，导致了侵袭性白血病表型的出现。在这里，各种Cre重组酶的表达导致了FLT3ITD/ITD祖细胞的多克隆扩张、分化阻滞的诱导和Myc依赖性基因表达程序的激活。我们的报告旨在提醒科学界使用这种特定的小鼠模型存在潜在风险，并在研究小鼠癌症模型中探究协同致癌基因突变时Cre表达的意外效应。 ©2023. 作者。

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 FLT3ITD/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.© 2023. The Author(s).