In vivo activity of ABT-869, a multi-target kinase inhibitor, against acute myeloid leukemia with wild-type FLT3 receptor.

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Zhou J, Khng J, Jasinghe VJ, Bi C, Neo CH, Pan M, Poon LF, Xie Z, Yu H, Yeoh AE, Lu Y, Glaser KB, Albert DH, Davidsen SK, Chen CS

In vivo activity of ABT-869, a multi-target kinase inhibitor, against acute myeloid leukemia with wild-type FLT3 receptor.

Leuk Res. 2008 Jul;32(7):1091-100. Epub 2007 Dec 26.

PubMed ID
18160102 [ View in PubMed
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Abstract

Neoangiogenesis plays an important role in leukemogenesis. We investigated the in vivo anti-leukemic effect of ABT-869 against AML with wild-type FLT3 using RFP transfected HL60 cells with in vivo imaging technology on both the subcutaneous and systemic leukemia xenograft models. ABT-869 showed a five-fold inhibition of tumor growth in comparison with vehicle control. IHC analysis revealed that ABT-869 decreased p-VEGFR1, Ki-67 labeling index, VEGF and remarkably increased apoptotic cells in the xenograft models. ABT-869 also reduced the leukemia burden and prolonged survival. Our study supports the rationale for clinically testing an anti-angiogenesis agent in AML with wild-type FLT3.

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