Cellular elements of the subarachnoid space promote ALL survival during chemotherapy

Leuk Res. 2011 Jun;35(6):705-11. doi: 10.1016/j.leukres.2010.12.031. Epub 2011 Jan 26.

Abstract

CNS infiltration by leukemic cells remains a problematic disease manifestation of acute lymphoblastic leukemia (ALL). Prophylactic regimens for CNS leukemia including intrathecal chemotherapeutics have decreased CNS involvement in ALL, but are not without toxicities. Using co-culture models, we show that astrocytes, choroid plexus epithelial cells, and meningeal cells protect ALL cells from chemotherapy-induced cell death using drugs included in prophylactic regimens-cytarabine, dexamethasone, and methotrexate. Understanding how ALL cells survive in the CNS remains invaluable for designing strategies to prevent CNS leukemia and minimizing the need for treatment in this sensitive anatomical site where treatment-induced toxicity is of significant concern.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Astrocytes / cytology
  • Astrocytes / drug effects
  • Cell Communication / drug effects
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cells, Cultured
  • Choroid Plexus / cytology
  • Coculture Techniques
  • Cytarabine / pharmacology*
  • Dexamethasone / pharmacology*
  • Dose-Response Relationship, Drug
  • Epithelial Cells / cytology
  • Epithelial Cells / drug effects
  • Humans
  • Meninges / cytology
  • Methotrexate / pharmacology*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / pathology
  • Subarachnoid Space / drug effects
  • Subarachnoid Space / pathology
  • Time Factors

Substances

  • Antineoplastic Agents
  • Cytarabine
  • Dexamethasone
  • Methotrexate