AML cells are differentially sensitive to chemotherapy treatment in a human xenograft model
As AML xenograft models improve, the potential for using them to evaluate novel therapeutic strategies becomes more appealing. Currently there is little information regarding the use of standard chemotherapy regimens in AML xenografts. Here we have characterized the immunodeficient mouse response to combined Ara-C and doxorubicin treatment. We observed significant toxicity associated with doxorubicin that required optimization of the route of injection as well as the maximum tolerable dose for immunodeficient strains. Mice treated with an optimized five-day induction protocol showed transient weight loss, short-term reduction of peripheral blood cell and platelet counts as well as slight anemia. Considerable cytotoxicity was observed in the bone marrow, with primitive LSK cells having a significant survival advantage relative to more mature cells, consistent with the idea of chemotherapy targeting actively growing cells. Treated leukemic mice demonstrated reduced disease burden and increased survival, demonstrating efficacy. AML cells showed significantly increased sensitivity to doxorubicin-containing therapy compared to murine BM cells. While early treatment could result in some cures, mice with significant leukemia grafts were not cured using induction therapy alone. Overall, the data show that this model system is useful for the evaluation of novel chemotherapies in combination with standard induction therapy.