CD47 is an adverse prognostic factor and therapeutic antibody target on human acute myeloid leukemia stem cells.
CD47 is an adverse prognostic factor and therapeutic antibody target on human acute myeloid leukemia stem cells.
复制标题
CD47是人类急性髓样白血病干细胞的不良预后因素和治疗抗体靶标。
DOI：
10.1016/j.cell.2009.05.045
复制
发表时间：
2009-07-23
期刊：
影响因子：
64.5
通讯作者：
Weissman IL
中科院分区：
文献类型：
--
作者：
Majeti R;Chao MP;Alizadeh AA;Pang WW;Jaiswal S;Gibbs KD Jr;van Rooijen N;Weissman IL
急性髓系白血病(AML)是由一组自我更新的白血病干细胞(LSC)启动和维持的细胞层次结构。我们推测，CD47在人AML LSC上的表达增加，通过CD47与吞噬细胞上的抑制受体相互作用来抑制其吞噬功能，从而参与了AML LSC的发病。我们发现CD47在AML LSC上的表达高于其正常对照，并且在3个独立的成人AML患者队列中，CD47表达的增加预示着总体预后较差。此外，针对CD47的封闭单抗优先促进AML LSC的吞噬作用，并抑制其体内植入。最后，用抗CD47抗体处理移植人AML LSC的小鼠，去除AML和靶向AML LSC。综上所述，CD47表达增加是一个独立的不良预后因素，可以通过阻断能够使LSC吞噬的单抗来靶向人类AML干细胞。
Acute myelogenous leukemia (AML) is organized as a cellular hierarchy initiated and maintained by a subset of self-renewing leukemia stem cells (LSC). We hypothesized that increased CD47 expression on human AML LSC contributes to pathogenesis by inhibiting their phagocytosis through the interaction of CD47 with an inhibitory receptor on phagocytes. We found that CD47 was more highly expressed on AML LSC than their normal counterparts, and that increased CD47 expression predicted worse overall survival in 3 independent cohorts of adult AML patients. Furthermore, blocking monoclonal antibodies directed against CD47 preferentially enabled phagocytosis of AML LSC and inhibited their engraftment in vivo. Finally, treatment of human AML LSC-engrafted mice with anti-CD47 antibody depleted AML and targeted AML LSC. In summary, increased CD47 expression is an independent poor prognostic factor that can be targeted on human AML stem cells with blocking monoclonal antibodies capable of enabling phagocytosis of LSC.
登录
查看更多内容
DOI：
10.1016/j.bbrc.2004.01.128
发表时间：
2004-03-19
影响因子：
3.1
作者：
Kikuchi, Y;Uno, S;Tsuchiya, M
通讯作者：
Tsuchiya, M
DOI：
10.1084/jem.194.4.541
发表时间：
2001-08-20
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Blazar BR;Lindberg FP;Ingulli E;Panoskaltsis-Mortari A;Oldenborg PA;Iizuka K;Yokoyama WM;Taylor PA
通讯作者：
Taylor PA
影响因子：
158.5
作者：
Jamieson, CHM;Ailles, LE;Weissman, IL
通讯作者：
Weissman, IL
影响因子：
20.3
作者：
Bullinger, Lars;Doehner, Konstanze;Pollack, Jonathan R.
通讯作者：
Pollack, Jonathan R.
DOI：
10.1073/pnas.0609661104
发表时间：
2007-03-20
影响因子：
11.1
作者：
Ide, Kentaro;Wang, Hui;Ohdan, Hideki
通讯作者：
Ohdan, Hideki