AML cells are differentially sensitive to chemotherapy treatment in a human xenograft model.

Abstract:

:As acute myeloid leukemia (AML) xenograft models improve, the potential for using them to evaluate novel therapeutic strategies becomes more appealing. Currently, there is little information on using standard chemotherapy regimens in AML xenografts. Here we have characterized the immunodeficient mouse response to combined Ara-C (cytarabine) and doxorubicin treatment. We observed significant toxicity associated with doxorubicin that required optimization of the route of injection as well as the maximum-tolerated dose for immunodeficient strains. Mice treated with an optimized 5-day induction protocol showed transient weight loss, short-term reduction of peripheral blood cell and platelet counts, and slight anemia. Considerable cytotoxicity was observed in the bone marrow (BM), 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 with murine BM cells. Although early treatment could result in some cures, mice with significant leukemia grafts were not cured by 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.

journal_name

Blood

journal_title

Blood

authors

Wunderlich M,Mizukawa B,Chou FS,Sexton C,Shrestha M,Saunthararajah Y,Mulloy JC

doi

10.1182/blood-2012-10-464677

subject

Has Abstract

pub_date

2013-03-21 00:00:00

pages

e90-7

issue

12

eissn

0006-4971

issn

1528-0020

pii

blood-2012-10-464677

journal_volume

121

pub_type

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