{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Brown AL"],"funding":["St. Baldrick&apos;s Foundation","National Cancer Institute","NCI NIH HHS","Leukemia Research Foundation","Cancer Prevention and Research Institute of Texas"],"pagination":["464-473"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC7914130"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["61(3)"],"pubmed_abstract":["<h4>Context</h4>Cancer-related fatigue (CRF) is one of the most distressing and persistent symptoms reported during pediatric acute lymphoblastic leukemia (ALL) therapy; however, information on the pathways underlying CRF severity is limited.<h4>Objectives</h4>We conducted global metabolomics profiling of cerebrospinal fluid (CSF) samples to provide insight into the underlying mechanisms of CRF.<h4>Methods</h4>Fatigue in pediatric ALL patients (2012-2017) was assessed during postinduction therapy approximately six months after diagnosis. Postinduction CSF was collected from 171 participants, comprising discovery (n = 86) and replication (n = 85) cohorts. We also conducted secondary validation using diagnostic CSF from 48 replication cohort participants. CSF metabolomic profiling was performed using gas chromatography-mass spectrometry (MS) and liquid chromatography-MS/MS. Kendall's rank correlation was used to evaluate associations between metabolite abundance and CRF. False discovery rate was used to account for multiple comparisons.<h4>Results</h4>Participants were 56% males and 59% Hispanic with a mean age at diagnosis of 8.5 years. A total of 274 CSF-derived metabolites were common to the discovery and replication cohorts. Eight metabolites were significantly associated with fatigue in the discovery cohort (P < 0.05), of which three were significant in the replication cohort, including false discovery rate-corrected associations with gamma-glutamylglutamine (P<sub>combined</sub> = 6.2E-6) and asparagine (P<sub>combined</sub> = 3.5E-4). Notably, the abundance of gamma-glutamylglutamine in diagnostic CSF samples was also significantly associated with fatigue (P = 0.0062).<h4>Conclusion</h4>The metabolites identified in our assessment have been implicated in neurotransmitter transportation and glutathione recycling, suggesting that glutamatergic pathways or oxidative stress may contribute to ALL-associated CRF. This information could inform targeted therapies for reducing CRF in at-risk individuals."],"journal":["Journal of pain and symptom management"],"pubmed_title":["Cerebrospinal Fluid Metabolomic Profiles Associated With Fatigue During Treatment for Pediatric Acute Lymphoblastic Leukemia."],"pmcid":["PMC7914130"],"funding_grant_id":["K07 CA218362"],"pubmed_authors":["Raghubar KP","Kahalley LS","Bernhardt MB","Scheurer ME","Hockenberry MJ","Woodhouse JP","Brown AL","Sok P","Taylor O","Lupo PJ"],"additional_accession":[]},"is_claimable":false,"name":"Cerebrospinal Fluid Metabolomic Profiles Associated With Fatigue During Treatment for Pediatric Acute Lymphoblastic Leukemia.","description":"<h4>Context</h4>Cancer-related fatigue (CRF) is one of the most distressing and persistent symptoms reported during pediatric acute lymphoblastic leukemia (ALL) therapy; however, information on the pathways underlying CRF severity is limited.<h4>Objectives</h4>We conducted global metabolomics profiling of cerebrospinal fluid (CSF) samples to provide insight into the underlying mechanisms of CRF.<h4>Methods</h4>Fatigue in pediatric ALL patients (2012-2017) was assessed during postinduction therapy approximately six months after diagnosis. Postinduction CSF was collected from 171 participants, comprising discovery (n = 86) and replication (n = 85) cohorts. We also conducted secondary validation using diagnostic CSF from 48 replication cohort participants. CSF metabolomic profiling was performed using gas chromatography-mass spectrometry (MS) and liquid chromatography-MS/MS. Kendall's rank correlation was used to evaluate associations between metabolite abundance and CRF. False discovery rate was used to account for multiple comparisons.<h4>Results</h4>Participants were 56% males and 59% Hispanic with a mean age at diagnosis of 8.5 years. A total of 274 CSF-derived metabolites were common to the discovery and replication cohorts. Eight metabolites were significantly associated with fatigue in the discovery cohort (P < 0.05), of which three were significant in the replication cohort, including false discovery rate-corrected associations with gamma-glutamylglutamine (P<sub>combined</sub> = 6.2E-6) and asparagine (P<sub>combined</sub> = 3.5E-4). Notably, the abundance of gamma-glutamylglutamine in diagnostic CSF samples was also significantly associated with fatigue (P = 0.0062).<h4>Conclusion</h4>The metabolites identified in our assessment have been implicated in neurotransmitter transportation and glutathione recycling, suggesting that glutamatergic pathways or oxidative stress may contribute to ALL-associated CRF. This information could inform targeted therapies for reducing CRF in at-risk individuals.","dates":{"release":"2021-01-01T00:00:00Z","publication":"2021 Mar","modification":"2025-04-05T14:05:42.822Z","creation":"2025-04-05T14:05:42.822Z"},"accession":"S-EPMC7914130","cross_references":{"pubmed":["32889041"],"doi":["10.1016/j.jpainsymman.2020.08.030"]}}