Central nervous system (CNS) relapse is a significant cause of treatment failure among patients with acute lymphoblastic leukemia. In prior work we found that the meninges, the thin layer of tissue that covers the brain and spinal cord, harbor leukemia cells in the CNS. Importantly, direct interactions between leukemia and meningeal cells enabled leukemia chemoresistance. Herein, we show that an antibody targeting CD99, a transmembrane protein expressed on meningeal cells and many leukemia cells, disrupts adhesion between leukemia and meningeal cells and restores sensitivity of the leukemia cells to chemotherapy. This work identifies a mechanism regulating critical intercellular interactions within the CNS leukemia niche and may lead to novel therapeutic approaches for overcoming niche-mediated chemoresistance.
Bibliographical noteFunding Information:
This work was supported by 1R37CA240846-01A1 (PMG), the Children’s Cancer Research Fund (PMG), and the Timothy O’Connell Foundation (PMG). This work utilized the University of Minnesota Masonic Cancer Center shared flow cytometry core which is supported in part by NCI 5P30CA077598-18, Minnesota Masonic Charities, and the Killebrew-Thompson Memorial Fund. Immunohistochemistry was performed by the Histology and Research Laboratory, part of the University of Minnesota Clinical and Translational Science Institute.
© 2021, The Author(s).