CD99 antibody disrupts T-cell acute lymphoblastic leukemia adhesion to meningeal cells and attenuates chemoresistance.
Maryam Ebadi, Leslie M Jonart, Jason Ostergaard, Peter M Gordon
Author Information
Maryam Ebadi: Division of Pediatric Hematology and Oncology, Department of Pediatrics, University of Minnesota, 420 Delaware St SE, MMC 366, Minneapolis, MN, 55455, USA.
Leslie M Jonart: Division of Pediatric Hematology and Oncology, Department of Pediatrics, University of Minnesota, 420 Delaware St SE, MMC 366, Minneapolis, MN, 55455, USA.
Jason Ostergaard: Division of Pediatric Hematology and Oncology, Department of Pediatrics, University of Minnesota, 420 Delaware St SE, MMC 366, Minneapolis, MN, 55455, USA.
Peter M Gordon: Division of Pediatric Hematology and Oncology, Department of Pediatrics, University of Minnesota, 420 Delaware St SE, MMC 366, Minneapolis, MN, 55455, USA. gord0047@umn.edu.
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.
