Zhou Jianbiao, Khng Jiaying, Jasinghe Viraj J, Bi Chonglei, Neo Chiew Hoon Serene, Pan Mengfei, Poon Lai Fong, Xie Zhigang, Yu Hanry, Yeoh Allen Eng-Juh, Lu Yi, Glaser Keith B, Albert Daniel H, Davidsen Steven K, Chen Chien-Shing
Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Leuk Res. 2008 Jul;32(7):1091-100. doi: 10.1016/j.leukres.2007.11.025. Epub 2007 Dec 26.
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.
新生血管生成在白血病发生过程中起重要作用。我们利用体内成像技术，在皮下和系统性白血病异种移植模型中，研究了ABT-869对具有野生型FLT3的急性髓系白血病（AML）的体内抗白血病作用。与载体对照相比，ABT-869显示出五倍的肿瘤生长抑制作用。免疫组化分析显示，在异种移植模型中，ABT-869降低了磷酸化血管内皮生长因子受体1（p-VEGFR1）、Ki-67标记指数、血管内皮生长因子（VEGF），并显著增加了凋亡细胞。ABT-869还减轻了白血病负担并延长了生存期。我们的研究支持了在具有野生型FLT3的AML中对一种抗血管生成药物进行临床试验的理论依据。
