title: In vivo activity of ABT-869, a multi-target kinase inhibitor, against acute myeloid leukemia with wild-type FLT3 receptor.
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.
authors.affiliation: Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors.forename: Jianbiao
authors.initials: J
authors.lastname: Zhou
authors.forename: Jiaying
authors.initials: J
authors.lastname: Khng
authors.forename: Viraj J
authors.initials: VJ
authors.lastname: Jasinghe
authors.forename: Chonglei
authors.initials: C
authors.lastname: Bi
authors.forename: Chiew Hoon Serene
authors.initials: CH
authors.lastname: Neo
authors.forename: Mengfei
authors.initials: M
authors.lastname: Pan
authors.forename: Lai Fong
authors.initials: LF
authors.lastname: Poon
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Xie
authors.forename: Hanry
authors.initials: H
authors.lastname: Yu
authors.forename: Allen Eng-Juh
authors.initials: AE
authors.lastname: Yeoh
authors.forename: Yi
authors.initials: Y
authors.lastname: Lu
authors.forename: Keith B
authors.initials: KB
authors.lastname: Glaser
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Albert
authors.forename: Steven K
authors.initials: SK
authors.lastname: Davidsen
authors.forename: Chien-Shing
authors.initials: CS
authors.lastname: Chen
mesh_terms: 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*
chemical_list: 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