CD98-Mediated Adhesive Signaling Enables the Establishment and Propagation of Acute Myelogenous Leukemia

被引：91

作者：

Bajaj, Jeevisha ^{[1
,2
,3
,4
]}

Konuma, Takaaki ^{[1
,2
,3
,4
]}

Lytle, Nikki K. ^{[1
,2
,3
,4
]}

Kwon, Hyog Young ^{[1
,2
,3
,4
]}

Ablack, Jailal N. ^{[4
]}

Cantor, Joseph M. ^{[4
]}

Rizzieri, David ^{[5
]}

Chuah, Charles ^{[6
]}

Oehler, Vivian G. ^{[7
]}

Broome, Elizabeth H. ^{[3
,8
]}

Ball, Edward D. ^{[3
,9
]}

van der Horst, Edward H. ^{[10
]}

Ginsberg, Mark H. ^{[3
,4
]}

Reya, Tannishtha ^{[1
,2
,3
,4
]}

机构：

[1] Univ Calif San Diego, Sch Med, Dept Pharmacol, La Jolla, CA 92093 USA

[2] Sanford Consortium Regenerat Med, La Jolla, CA 92037 USA

[3] Univ Calif San Diego, Sch Med, Moores Canc Ctr, La Jolla, CA 92093 USA

[4] Univ Calif San Diego, Sch Med, Dept Med, La Jolla, CA 92093 USA

[5] Duke Univ, Med Ctr, Dept Med, Div Cell Therapy, Durham, NC 27710 USA

[6] Singapore Gen Hosp, Canc & Stem Cell Biol Program, Duke NUS Grad Med Sch, Dept Haematol, Singapore 169857, Singapore

[7] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98109 USA

[8] Univ Calif San Diego, Sch Med, Dept Pathol, La Jolla, CA 92093 USA

[9] Univ Calif San Diego, Sch Med, Dept Med, Blood & Marrow Transplantat Div, La Jolla, CA 92093 USA

[10] Igenica Biotherapeut Inc, Burlingame, CA 94010 USA

来源：

CANCER CELL | 2016年 / 30卷 / 05期

关键词：

ACUTE MYELOID-LEUKEMIA; HEMATOPOIETIC STEM-CELLS; THERAPEUTIC TARGETS; IN-VIVO; KAPPA-B; CANCER; GROWTH; CD98; ACTIVATION; SURVIVAL;

D O I：

10.1016/j.ccell.2016.10.003

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Acute myelogenous leukemia (AML) is an aggressive disease associated with drug resistance and relapse. To improve therapeutic strategies, it is critical to better understand the mechanisms that underlie AML progression. Here we show that the integrin binding glycoprotein CD98 plays a central role in AML. CD98 promotes AML propagation and lethality by driving engagement of leukemia cells with their microenvironment and maintaining leukemic stem cells. Further, delivery of a humanized anti-CD98 antibody blocks growth of patient -derived AML, highlighting the importance of this pathway in human disease. These findings indicate that microenvironmental interactions are key regulators of AML and that disrupting these signals with targeted inhibitors such as CD98 antibodies may be a valuable therapeutic approach for adults and children with this disease.

引用

页码：792 / 805

页数：14

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