Changes in Oxidant Defense, Apoptosis, and Cognitive Abilities During Treatment for Childhood Leukemia

Ida M Moore, Kari M. Koerner, Patricia M. Gundy, David W Montgomery, Kathleen C Insel, Lynnette L. Harris, Olga A. Taylor, Marilyn J. Hockenberry

Research output: Contribution to journalArticle

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Abstract

Aggressive central nervous system (CNS)-directed treatment for acute lymphoblastic leukemia (ALL), the most prevalent cancer among children and adolescents, prevents metastasis of leukemia cells into the brain. Up to 60% of survivors experience cognitive problems, but knowledge about risk factors for and mechanisms of neurologic injury is lacking. Objectives of the present study were to (1) quantify changes in oxidant defense and apoptosis over the course of ALL therapy and (2) elucidate risk factors for long-term cognitive problems. The sample included 71 children with ALL. Cerebrospinal fluid (CSF) samples were collected at diagnosis and during intrathecal chemotherapy administration. Oxidant defense was measured by reduced glutathione (GSH), oxidized glutathione (GSSG), and the ratio of GSH:GSSG. Apoptosis was measured by activity of several cysteine-dependent aspartate-specific protease (abbreviated as caspase) enzymes that initiate (caspases 8 and 9) or execute (caspases 3/7) apoptosis. Cognitive abilities were assessed by standardized measures of short-term memory, visual-motor integration, and attention 3 years after ALL diagnosis. GSH and GSSG concentration increased significantly during ALL therapy, and a low GSH:GSSG ratio was indicative of an oxidized extracellular environment. Caspase enzyme activity increased significantly, and caspases 3/7 activity was significantly and negatively associated with performance on measures of cognitive abilities. Younger age at time of ALL diagnosis was associated with some measures of attention. Efflux of glutathione into CSF maintains oxidant defense by scavenging free radicals and other reactive oxygen species and is an early event in apoptosis. These mechanisms may be involved in neurologic injury associated with CNS-directed treatment and subsequent cognitive problems.

Original languageEnglish (US)
JournalBiological Research for Nursing
DOIs
StateAccepted/In press - Jan 1 2018

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Aptitude
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Glutathione Disulfide
Oxidants
Leukemia
Apoptosis
Nervous System Trauma
Caspase 7
Caspases
Caspase 3
Glutathione
Cerebrospinal Fluid
Therapeutics
Central Nervous System
Caspase 9
Caspase 8
Enzymes
Short-Term Memory
Aspartic Acid
Free Radicals

Keywords

  • apoptosis
  • caspase enzymes
  • cognitive abilities
  • glutathione
  • oxidant defense

ASJC Scopus subject areas

  • Research and Theory

Cite this

Changes in Oxidant Defense, Apoptosis, and Cognitive Abilities During Treatment for Childhood Leukemia. / Moore, Ida M; Koerner, Kari M.; Gundy, Patricia M.; Montgomery, David W; Insel, Kathleen C; Harris, Lynnette L.; Taylor, Olga A.; Hockenberry, Marilyn J.

In: Biological Research for Nursing, 01.01.2018.

Research output: Contribution to journalArticle

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