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

Publication date: Available online 27 October 2016
Source:Cancer Cell
Author(s): Jeevisha Bajaj, Takaaki Konuma, Nikki K. Lytle, Hyog Young Kwon, Jailal N. Ablack, Joseph M. Cantor, David Rizzieri, Charles Chuah, Vivian G. Oehler, Elizabeth H. Broome, Edward D. Ball, Edward H. van der Horst, Mark H. Ginsberg, Tannishtha Reya
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.

Graphical abstract

Teaser

Bajaj et al. demonstrate the importance of CD98-mediated adhesion for survival of acute myelogenous leukemia (AML) and show that genetic deletion of CD98 in mice or use of a therapeutic CD98 antibody in patient-derived xenografts blocks AML growth.


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