Patient-derived xenografts for pre-clinical drug development in AML

Introduction:

A potential strategy to improve the efficacy of drug development and patient outcomes could be selecting the 'right' treatment in pre-clinical studies performed in patient-derived xenografts (PDXs). In acute myeloid leukemia (AML) establishment of appropriate pre-clinical models with specific mutational types remains a major challenge.

Results:

Using immunodeficient mice, NOD.Cg-Prkdc^scidIl2rg^tm1Wjl/SzJ (NSG) and more receptible humanized knock-in mice, we have successfully established a PDX-xenobank consisting of various AML mutational phenotypes. The PDX-xenobank contains a large number of transplantable MLL-r leukemias and myeloid leukemias in Down syndrome (ML-DS).

Conclusion:

PDX models are a relevant pre-clinical platform in AML research, as they more accurately reflect human mutational specific biology than any other existing models. If PDXs are viewed as complementary to other experimental models, the use of PDXs should lead to a higher rate of success in identifying new and more effective therapeutic strategies and in transitioning into individualized therapy.