Cerebrospinal Fluid Biomarkers in Childhood Leukemias

SIMPLE SUMMARY: In childhood leukemias the central nervous system (CNS) can be invaded by leukemic cells, leading to disease recurrence and treatment failures. Analysis of the cerebrospinal fluid (CSF), which surrounds the brain and spinal cord, is crucial for detection of leukemia in that compartment. Despite advances made in treatments for childhood leukemias, therapies continue to adversely affect the developing brain with resulting neurocognitive deficits in many survivors. This review presents an overview of studies demonstrating that CSF proteins, nucleic acids and metabolites, so called biomarkers, can be utilized in tracing both CNS disease and neurotoxicity of treatments in childhood leukemias. ABSTRACT: Involvement of the central nervous system (CNS) in childhood leukemias remains a major cause of treatment failures. Analysis of the cerebrospinal fluid constitutes the most important diagnostic pillar in the detection of CNS leukemia and relies primarily on cytological and flow-cytometry studies. With increasing survival rates, it has become clear that treatments for pediatric leukemias pose a toll on the developing brain, as they may cause acute toxicities and persistent neurocognitive deficits. Preclinical research has demonstrated that established and newer therapies can injure and even destroy neuronal and glial cells in the brain. Both passive and active cell death forms can result from DNA damage, oxidative stress, cytokine release, and acceleration of cell aging. In addition, chemotherapy agents may impair neurogenesis as well as the function, formation, and plasticity of synapses. Clinical studies show that neurocognitive toxicity of chemotherapy is greatest in younger children. This raises concerns that, in addition to injury, chemotherapy may also disrupt crucial developmental events resulting in impairment of the formation and efficiency of neuronal networks. This review presents an overview of studies demonstrating that cerebrospinal fluid biomarkers can be utilized in tracing both CNS disease and neurotoxicity of administered treatments in childhood leukemias.