Dataset Information

Comparison of the blood, bone marrow, and cerebrospinal fluid metabolomes in children with b-cell acute lymphoblastic leukemia.

ABSTRACT: Metabolomics may shed light on treatment response in childhood acute lymphoblastic leukemia (ALL), however, most assessments have analyzed bone marrow or cerebrospinal fluid (CSF), which are not collected during all phases of therapy. Blood is collected frequently and with fewer risks, but it is unclear whether findings from marrow or CSF biomarker studies may translate. We profiled end-induction plasma, marrow, and CSF from N = 10 children with B-ALL using liquid chromatography-mass spectrometry. We estimated correlations between plasma and marrow/CSF metabolite abundances detected in ≥ 3 patients using Spearman rank correlation coefficients (r_s). Most marrow metabolites were detected in plasma (N = 661; 81%), and we observed moderate-to-strong correlations (median r_s 0.62, interquartile range [IQR] 0.29-0.83). We detected 328 CSF metabolites in plasma (90%); plasma-CSF correlations were weaker (median r_s 0.37, IQR 0.07-0.70). We observed plasma-marrow correlations for metabolites in pathways associated with end-induction residual disease (pyruvate, asparagine) and plasma-CSF correlations for a biomarker of fatigue (gamma-glutamylglutamine). There is considerable overlap between the plasma, marrow, and CSF metabolomes, and we observed strong correlations for biomarkers of clinically relevant phenotypes. Plasma may be suitable for biomarker studies in B-ALL.

SUBMITTER: Schraw JM

PROVIDER: S-EPMC8490393 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

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Comparison of the blood, bone marrow, and cerebrospinal fluid metabolomes in children with b-cell acute lymphoblastic leukemia.

Schraw Jeremy M JM Woodhouse J P JP Bernhardt Melanie B MB Taylor Olga A OA Horton Terzah M TM Scheurer Michael E ME Okcu M Fatih MF Rabin Karen R KR Lupo Philip J PJ Brown Austin L AL

Scientific reports 20211004 1

Metabolomics may shed light on treatment response in childhood acute lymphoblastic leukemia (ALL), however, most assessments have analyzed bone marrow or cerebrospinal fluid (CSF), which are not collected during all phases of therapy. Blood is collected frequently and with fewer risks, but it is unclear whether findings from marrow or CSF biomarker studies may translate. We profiled end-induction plasma, marrow, and CSF from N = 10 children with B-ALL using liquid chromatography-mass spectrometr ...[more]

PMID: 34608220

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Project description:ContextCancer-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.ObjectivesWe conducted global metabolomics profiling of cerebrospinal fluid (CSF) samples to provide insight into the underlying mechanisms of CRF.MethodsFatigue 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.ResultsParticipants 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 (Pcombined = 6.2E-6) and asparagine (Pcombined = 3.5E-4). Notably, the abundance of gamma-glutamylglutamine in diagnostic CSF samples was also significantly associated with fatigue (P = 0.0062).ConclusionThe 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.

Dataset Information

Comparison of the blood, bone marrow, and cerebrospinal fluid metabolomes in children with b-cell acute lymphoblastic leukemia.

Publications

Comparison of the blood, bone marrow, and cerebrospinal fluid metabolomes in children with b-cell acute lymphoblastic leukemia.

Similar Datasets

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