The meninges enhance leukaemia survival in cerebral spinal fluid

Patrick Basile, Leslie M. Jonart, Maryam Ebadi, Kimberly Johnson, Morgan Kerfeld, Peter M. Gordon

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Central nervous system (CNS) relapse is a common cause of treatment failure in patients with acute lymphoblastic leukaemia (ALL) despite current CNS-directed therapies that are also associated with significant short- and long-term toxicities. Herein, we showed that leukaemia cells exhibit decreased proliferation, elevated reactive oxygen species (ROS) and increased cell death in cerebral spinal fluid (CSF) both in vitro and in vivo. However, interactions between leukaemia and meningeal cells mitigated these adverse effects. This work expands our understanding of the pathophysiology of CNS leukaemia and suggests novel therapeutic approaches for more effectively targeting leukaemia cells in the CNS.

Original languageEnglish (US)
Pages (from-to)513-517
Number of pages5
JournalBritish journal of haematology
Volume189
Issue number3
DOIs
StatePublished - May 1 2020

Bibliographical note

Funding Information:
Patrick Basile Leslie M. Jonart Maryam Ebadi Kimberly Johnson Morgan Kerfeld Peter M. Gordon gord0047@umn.edu Division of Pediatric Hematology and Oncology Department of Pediatrics University of Minnesota Minneapolis MN USA Masonic Cancer Center University of Minnesota Minneapolis MN USA acute lymphpoblastic leukaemia central nervous system cerebral spinal fluid cell death cell adhesion Childrenɹs Cancer Research Fund Timothy O'Connell Foundation American Cancer Society Institutional Research NIH T32 CA099936 Figure S1. Direct leukaemia–meningeal contact is required to enhance leukaemia cell survival in CSF. Figure S2. Disrupting leukaemia–meningeal adhesion in CSF increases leukaemia cell death.

Funding Information:
This work was supported in part by the Children's Cancer Research Fund (PMG), the Timothy O'Connell Foundation (PMG) and an American Cancer Society Institutional Research Grant (PMG). PB was partially supported by NIH Training Grant T32 CA099936.

Funding Information:
This work was supported in part by the Children's Cancer Research Fund (PMG), the Timothy O'Connell Foundation (PMG) and an American Cancer Society Institutional Research Grant (PMG). PB was partially supported by NIH Training Grant T32 CA099936.

Publisher Copyright:
© 2020 British Society for Haematology and John Wiley & Sons Ltd

Keywords

  • acute lymphpoblastic leukaemia
  • cell adhesion
  • cell death
  • central nervous system
  • cerebral spinal fluid

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

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