In vivo activity of ABT-869, a multi-target kinase inhibitor, against acute myeloid leukemia with wild-type FLT3 receptor.
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.
Zhou
Jianbiao
J
Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Khng
Jiaying
J
Jasinghe
Viraj J
VJ
Bi
Chonglei
C
Neo
Chiew Hoon Serene
CH
Pan
Mengfei
M
Poon
Lai Fong
LF
Xie
Zhigang
Z
Yu
Hanry
H
Yeoh
Allen Eng-Juh
AE
Lu
Yi
Y
Glaser
Keith B
KB
Albert
Daniel H
DH
Davidsen
Steven K
SK
Chen
Chien-Shing
CS
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D016026:Bone Marrow Transplantation; D018922:HL-60 Cells; D006801:Humans; D007191:Indazoles / Q000627:therapeutic use*; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000378:metabolism; D010671:Phenylurea Compounds / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D014183:Transplantation, Heterologous; D051941:fms-Like Tyrosine Kinase 3 / Q000378:metabolism*
D000970:Antineoplastic Agents; D007191:Indazoles; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; C513486:linifanib; C497970:FLT3 protein, human; D020794:Receptor Protein-Tyrosine Kinases; D051941:fms-Like Tyrosine Kinase 3