CD47 Is an Adverse Prognostic Factor and Therapeutic Antibody Target on Human Acute Myeloid Leukemia Stem Cells

被引：1454

作者：

Majeti, Ravindra ^{[1
,3
,4
]}

Chao, Mark P. ^{[3
,4
]}

Alizadeh, Ash A. ^{[1
,3
,4
]}

Pang, Wendy W. ^{[3
,4
]}

Jaiswal, Siddhartha ^{[3
,4
]}

Gibbs, Kenneth D., Jr. ^{[5
,6
]}

van Rooijen, Nico ^{[7
]}

Weissman, Irving L. ^{[2
,3
,4
]}

机构：

[1] Stanford Univ, Div Hematol, Dept Internal Med, Palo Alto, CA 94304 USA

[2] Stanford Univ, Dept Pathol, Palo Alto, CA 94304 USA

[3] Stanford Univ, Stanford Canc Ctr, Inst Stem Cell Biol & Regenerat Med, Palo Alto, CA 94304 USA

[4] Stanford Univ, Ludwig Ctr Stanford, Palo Alto, CA 94304 USA

[5] Stanford Univ, Program Immunol, Palo Alto, CA 94304 USA

[6] Stanford Univ, Baxter Lab Genet Pharmacol, Palo Alto, CA 94304 USA

[7] Vrije Univ Amsterdam, VUMC, Dept Mol Cell Biol, Amsterdam, Netherlands

来源：

CELL | 2009年 / 138卷 / 02期

基金：

美国国家卫生研究院; 美国国家科学基金会;

关键词：

ACUTE MYELOGENOUS LEUKEMIA; SIGNAL-REGULATORY PROTEIN; RECEPTOR-ALPHA CHAIN; MONOCLONAL-ANTIBODY; DENDRITIC CELL; SIRP-ALPHA; NEGATIVE REGULATION; CANCER; PROGENITORS; MARKER;

D O I：

10.1016/j.cell.2009.05.045

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Acute myeloid 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 three 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.

引用

页码：286 / 299

页数：14

共 46 条

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