Cerebrospinal Fluid Biomarkers 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.

Application of Metabolomics in Childhood Leukemia Diagnostics

“…The need to understand the causes of metastasis and predict their possible occurrence seems to be a priority task. The attempt to solve this problem most probably is going to be based primarily on molecular biology analysis techniques (Hess et al 2014 ; Ikonomidou 2021 ; Kuehnbaum and Britz-McKibbin 2013 ). Examination of the CSF remains, despite the development of neuroimaging techniques, an essential component of neurological diagnostics.…”

Clinical Proteomics of Biofluids in Haematological Malignancies

“…The incidence of CNS involvement is relatively rare but differs depending on the blood cancer subtype. Around 1% of myeloma patients and between 3 and 5% of childhood leukaemia patients have CNS involvement [ 164 , 165 ]. Cytological assessment of CSF to detect CNS involvement suffers from low sensitivity due to contamination with peripheral blood cells and the presence of disease at undetectable levels [ 166 ].…”

“…However, a study incorporating a larger cohort and longitudinal sampling may reveal significant proteomic changes in the CSF of ALL patients analysed before and during CNS infiltration [ 167 ]. CSF-based biomarkers in childhood leukaemias have recently been reviewed [ 164 ]. A recent study revealed soluble interleukin-2 receptor (IL-2R) levels in CSF as a useful diagnostic indicators of CNS infiltration in haematological malignancies, with the combined analysis of soluble IL-2R and autotaxin improving detection sensitivity in patients with lymphoma [ 163 ].…”

Taper up-off treatment of opium may reverse some dysregulations of gene expression patterns caused by four type of leukemia, AML, ALL, CML and CLL; a pilot animal model study

“…are reported as risk factors of leukemia. 5 Different types of chemotherapeutic drugs, radiation therapy, targeted therapy, and bone marrow transplant, alone or in combination with each other are currently using for treatment of leukemia. 6 In addition, the Immunotherapy which prompts the immune system to identify and destroy cancerous cells is most novel treatment for leukemia.…”