Apatinib exhibits anti-leukemia activity in preclinical models of acute lymphoblastic leukemia

• DOI: 10.1186/s12967-018-1421-y
• Publication Date: 2018-02-28T16:15:22Z
• Authors: Manman Deng; Jie Zha; Zhiwu Jiang; Xian Jia; Yuanfei Shi; Peng Li; Xiao Lei Chen; Zhihong Fang; Zhiqiang Du; Bing Xu
• Keywords: Apatinib; Mass cytometry

Acute lymphoblastic leukemia (ALL) is a clonal malignant disorder characterized by an uncontrolled proliferation of immature B or T lymphocytes. Extensive studies have suggested involvement angiogenesis signaling in ALL progression and resistance to treatment. Thus, targeting with anti-angiogenic drugs may be promising approach for In this study, we investigated the effectiveness Apatinib, novel receptor tyrosine kinase inhibitor selectively VEGFR-2 cells. cell lines were treated different concentration Apatinib then CCK8 assay, flow cytometry used determine IC50 value apoptosis, respectively. The effect against primary cells from 11 adult patients normal counterparts also analyzed apoptosis cytometry. Next, western bolting mass (CyTOF) assay explore underlying mechanism cytotoxicity Apatinib. Finally, anti-leukemia activity was further evaluated vivo xenograft model ALL. Our results showed that significantly inhibited growth promoted both lineage dose- time-dependent manner. values Nalm6, Reh, Jurkat Molt4 48 h 55.76 ± 13.19, 51.53 10.74, 32.43 5.58, 39.91 9.88 μmol/L, 72 30.34 2.65, 31.96 3.92, 17.62 5.90, 17.65 2.17 μmol/L Similarly, shows cytotoxic while sparing their vitro. Moreover, suppressed model. Mechanistically, Apatinib-induced closely associated inhibition VEGFR2 its downstream cascades, including PI3 K, MAPK STAT3 pathways. study indicates exerts inducing through suppressing pathway, supporting potential role treatment