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

Cancer Cell. 2016 Nov 14;30(5):792-805. doi: 10.1016/j.ccell.2016.10.003. Epub 2016 Oct 27.

Abstract

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.

Keywords: CD98; SLC3A2; acute myelogenous leukemia; adhesion; cancer; cancer stem cell; imaging; integrin; leukemia; microenvironment.

Publication types

  • Comment

MeSH terms

  • Animals
  • Antibodies / administration & dosage*
  • Antibodies / pharmacology
  • Cell Adhesion
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Fusion Regulatory Protein-1 / antagonists & inhibitors
  • Fusion Regulatory Protein-1 / genetics*
  • Gene Knockout Techniques
  • Humans
  • Leukemia, Myeloid, Acute / drug therapy*
  • Leukemia, Myeloid, Acute / genetics
  • Leukemia, Myeloid, Acute / pathology
  • Mice
  • Neoplasm Transplantation
  • Neoplastic Stem Cells / pathology*

Substances

  • Antibodies
  • Fusion Regulatory Protein-1