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. doi: 10.1016/j.leukres.2007.11.025. Epub 2007 Dec 26.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / therapeutic use*
  • Bone Marrow Transplantation
  • HL-60 Cells
  • Humans
  • Indazoles / therapeutic use*
  • Leukemia, Myeloid, Acute / drug therapy*
  • Leukemia, Myeloid, Acute / metabolism
  • Phenylurea Compounds / therapeutic use*
  • Protein Kinase Inhibitors / therapeutic use*
  • Receptor Protein-Tyrosine Kinases / antagonists & inhibitors
  • Transplantation, Heterologous
  • fms-Like Tyrosine Kinase 3 / metabolism*

Substances

  • Antineoplastic Agents
  • Indazoles
  • Phenylurea Compounds
  • Protein Kinase Inhibitors
  • linifanib
  • FLT3 protein, human
  • Receptor Protein-Tyrosine Kinases
  • fms-Like Tyrosine Kinase 3