Wang Ying-Chao, Feng Lei, Yin Chu-Yun, Ma Li-Na, Wei Yong-Wei, Wang Chun-Mei, Sheng Guang-Yao
Department of Pediatrics, First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
Zhongguo Dang Dai Er Ke Za Zhi. 2013 Jul;15(7):577-82.
To study the prognostic significance of CD47 in a NOD/SCID mouse model of acute myeloid leukemia (AML) and the best strategy for targeted therapy for this disease.
CD34(+)CD38(-) leukemia stem cells (LSCs) were separated and transplanted into NOD/SCID mice to establish a mouse model of acute monocytic leukemia (AMoL). Anti-human CD47 antibody, alone or combined with cytosine arabinoside (Ara-C), was used to treat the mice with AMoL for 7-14 days, and therapeutic efficacy was assessed. LSCs were cultured together with mouse macrophages in culture medium containing anti-CD47 or anti-CD45 monoclonal antibody for 2 hours, to observe the phagocytic ability of macrophages to LSCs.
CD34(+)CD38(-) LSCs existed among THP-1 cells, with a content of about (0.12 ± 0.06)%, and a mouse model of AML was successfully established after the purified CD34(+)CD38(-) LSCs (97.0% ± 1.7%) were transplanted into NOD/SCID mice. The in vivo experiment showed that mice with AMoL had the most significant decrease in CD33(+)CD45(+) leukemia cells in peripheral blood and bone marrow and survived the longest after being treated with Ara-C (7 days) plus anti-CD47 monoclonal antibody (14 days) (P < 0.01). After 2 hours of in vitro culture, the phagocytic index in the culture medium containing anti-CD47 monoclonal antibody was significantly higher than in the culture medium containing anti-CD45 monoclonal antibody (76.9% ± 12.2% vs 7.60% ± 2.4%; P < 0.05).
High expression of CD47 is an adverse prognostic factor in AML. Combination therapy with anti-CD47 monoclonal antibody and Ara-C can effectively eliminate leukemia cells and LSCs, demonstrating great clinical significance in curing AML.
研究CD47在急性髓系白血病（AML）的NOD/SCID小鼠模型中的预后意义以及针对该疾病的最佳靶向治疗策略。
分离CD34(+)CD38(-)白血病干细胞（LSCs）并将其移植到NOD/SCID小鼠中，以建立急性单核细胞白血病（AMoL）小鼠模型。单独使用抗人CD47抗体或与阿糖胞苷（Ara-C）联合使用，对AMoL小鼠进行7至14天的治疗，并评估治疗效果。将LSCs与小鼠巨噬细胞在含有抗CD47或抗CD45单克隆抗体的培养基中共同培养2小时，以观察巨噬细胞对LSCs的吞噬能力。
THP-1细胞中存在CD34(+)CD38(-) LSCs，含量约为(0.12±0.06)%，将纯化的CD34(+)CD38(-) LSCs（97.0%±1.7%）移植到NOD/SCID小鼠后成功建立了AML小鼠模型。体内实验表明，AMoL小鼠在用Ara-C（7天）加抗CD47单克隆抗体（14天）治疗后，外周血和骨髓中CD33(+)CD45(+)白血病细胞减少最为显著，存活时间最长（P<0.01）。体外培养2小时后，含有抗CD47单克隆抗体的培养基中的吞噬指数明显高于含有抗CD45单克隆抗体的培养基（76.9%±12.2%对7.60%±2.4%；P<0.05）。
CD47的高表达是AML的不良预后因素。抗CD47单克隆抗体与Ara-C联合治疗可有效清除白血病细胞和LSCs，在治愈AML方面具有重大临床意义。
