Pengcheng Shi1, Leisi Zhang1, Kai Chen1, Zhiwu Jiang2, Manman Deng3, Jie Zha3, Xutao Guo1, Peng Li2, Bing Xu3. 1. Department of Hematology, Nanfang Hospital, Southern Medical University, 510515 Guangzhou, China. 2. Key Laboratory of Regenerative Biology, South China Institute for Stem Cell Biology & Regenerative Medicine, Guangzhou Institutes of Biomedicine & Health, Chinese Academy of Sciences, Guangzhou 510530, China. 3. Department of Hematology, The First Affiliated Hospital of Xiamen University, Xiamen 361003, China.
Abstract
AIM: To investigate the combined action of decitabine (DAC) with chidamide (CS055) on acute lymphoblastic leukemia (ALL) cells. MATERIALS & METHODS: ALL cell lines as well as primary cells from 17 ALL patients were subjected to different treatments and thereafter cell counting Kit-8 (CCK-8) assay, flow cytometry and western blot were employed to determine IC50, apoptosis and checkpoint kinase 1 and γH2A.X expression. RESULTS: Low-dose DAC combined with CS055 could effectively kill ALL cells by the reduction of cell viability and induction of apoptosis. This was also observed in primary cells from 17 ALL patients, especially for those with p16 gene deletion. Suppression of checkpoint kinase 1 phosphorylation and upregulation of γH2A.X expression was demonstrated to participate in DAC plus CS055-induced apoptosis. CONCLUSION: Low-dose DAC could enhance chidamide-induced apoptosis in adult ALL, especially for patients with p16 gene deletion through DNA damage.
AIM: To investigate the combined action of decitabine (DAC) with chidamide (CS055) on acute lymphoblastic leukemia (ALL) cells. MATERIALS & METHODS: ALL cell lines as well as primary cells from 17 ALL patients were subjected to different treatments and thereafter cell counting Kit-8 (CCK-8) assay, flow cytometry and western blot were employed to determine IC50, apoptosis and checkpoint kinase 1 and γH2A.X expression. RESULTS: Low-dose DAC combined with CS055 could effectively kill ALL cells by the reduction of cell viability and induction of apoptosis. This was also observed in primary cells from 17 ALL patients, especially for those with p16 gene deletion. Suppression of checkpoint kinase 1 phosphorylation and upregulation of γH2A.X expression was demonstrated to participate in DAC plus CS055-induced apoptosis. CONCLUSION: Low-dose DAC could enhance chidamide-induced apoptosis in adult ALL, especially for patients with p16 gene deletion through DNA damage.
Authors: C Roolf; A Richter; C Konkolefski; G Knuebel; A Sekora; S Krohn; J Stenzel; B J Krause; B Vollmar; H Murua Escobar; C Junghanss Journal: J Hematol Oncol Date: 2018-05-04 Impact factor: 17.388