THP1细胞系
CD47型
阿糖胞苷
单克隆抗体
白血病
急性单核细胞白血病
人口
抗体
体外
体内
边居
干细胞
单核细胞白血病
免疫学
单克隆
癌症研究
细胞培养
医学
生物
癌症干细胞
细胞生物学
生物化学
生物技术
环境卫生
遗传学
作者
Y Wang,Yin C,Lei Feng,Chuo Wang,Guang-Yao Sheng
出处
期刊:Genetics and Molecular Research
[Genetics and Molecular Research]
日期:2015-01-01
卷期号:14 (2): 5630-5641
被引量:23
标识
DOI:10.4238/2015.may.25.15
摘要
Leukemia stem cells (LSCs) are regarded as the origin of leukemia and its recurrence. Side population (SP) cells possess some intrinsic stem cell properties and contain numerous LSCs. In this study, we examined the prognostic significance of cluster differentiation 47 (CD47) and identified the appropriate target for eliminating LSCs. We determined the percentage of SP cells in a THP-1 cell population and analyzed CD47 expression in different cell subsets. We then explored whether CD47 affected the phagocytic ability of macrophages to LSCs in vitro. Finally, the effect of anti-CD47 monoclonal antibodies, alone or combination with cytarabine, against leukemic cells was evaluated in vitro and in vivo to identify the optimal targets for the treatment of leukemia. We observed an SP sub-fraction at low frequency (1.81 ± 0.99%), which was a likely candidate for LSC enrichment. CD47 was more highly expressed on THP-1 LSCs (P < 0.05) and was an independent predictor of survival and refractory disease in THP-1-engrafted mice. Furthermore, the anti-CD47 monoclonal antibody stimulated preferential phagocytosis of LSCs by macrophages in vitro. Finally, single or combination treatment of THP-1 LSC-engrafted mice with cytarabine and anti-CD47 antibody resulted in targeting of LSCs and depletion of leukemia cells. These findings suggest that CD47 is an antibody target in LSCs and combination treatment with cytarabine and anti-CD47 monoclonal antibody represents an attractive option for the therapeutic targeting of acute monocytic leukemia.
科研通智能强力驱动
Strongly Powered by AbleSci AI