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...

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Main Authors: Jeremy M. Schraw, J. P. Woodhouse, Melanie B. Bernhardt, Olga A. Taylor, Terzah M. Horton, Michael E. Scheurer, M. Fatih Okcu, Karen R. Rabin, Philip J. Lupo, Austin L. Brown
Format: Article
Language:English
Published: Nature Portfolio 2021-10-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-021-99147-6
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author Jeremy M. Schraw
J. P. Woodhouse
Melanie B. Bernhardt
Olga A. Taylor
Terzah M. Horton
Michael E. Scheurer
M. Fatih Okcu
Karen R. Rabin
Philip J. Lupo
Austin L. Brown
author_facet Jeremy M. Schraw
J. P. Woodhouse
Melanie B. Bernhardt
Olga A. Taylor
Terzah M. Horton
Michael E. Scheurer
M. Fatih Okcu
Karen R. Rabin
Philip J. Lupo
Austin L. Brown
author_sort Jeremy M. Schraw
collection DOAJ
description 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.
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spelling doaj.art-8c04e83546a4413485aff2fad63ba6372022-12-21T19:27:58ZengNature PortfolioScientific Reports2045-23222021-10-011111810.1038/s41598-021-99147-6Comparison of the blood, bone marrow, and cerebrospinal fluid metabolomes in children with b-cell acute lymphoblastic leukemiaJeremy M. Schraw0J. P. Woodhouse1Melanie B. Bernhardt2Olga A. Taylor3Terzah M. Horton4Michael E. Scheurer5M. Fatih Okcu6Karen R. Rabin7Philip J. Lupo8Austin L. Brown9Section of Hematology-Oncology, Department of Pediatrics, Baylor College of MedicineSection of Hematology-Oncology, Department of Pediatrics, Baylor College of MedicineSection of Hematology-Oncology, Department of Pediatrics, Baylor College of MedicineSection of Hematology-Oncology, Department of Pediatrics, Baylor College of MedicineSection of Hematology-Oncology, Department of Pediatrics, Baylor College of MedicineSection of Hematology-Oncology, Department of Pediatrics, Baylor College of MedicineSection of Hematology-Oncology, Department of Pediatrics, Baylor College of MedicineSection of Hematology-Oncology, Department of Pediatrics, Baylor College of MedicineSection of Hematology-Oncology, Department of Pediatrics, Baylor College of MedicineSection of Hematology-Oncology, Department of Pediatrics, Baylor College of MedicineAbstract 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.https://doi.org/10.1038/s41598-021-99147-6
spellingShingle Jeremy M. Schraw
J. P. Woodhouse
Melanie B. Bernhardt
Olga A. Taylor
Terzah M. Horton
Michael E. Scheurer
M. Fatih Okcu
Karen R. Rabin
Philip J. Lupo
Austin L. Brown
Comparison of the blood, bone marrow, and cerebrospinal fluid metabolomes in children with b-cell acute lymphoblastic leukemia
Scientific Reports
title Comparison of the blood, bone marrow, and cerebrospinal fluid metabolomes in children with b-cell acute lymphoblastic leukemia
title_full Comparison of the blood, bone marrow, and cerebrospinal fluid metabolomes in children with b-cell acute lymphoblastic leukemia
title_fullStr Comparison of the blood, bone marrow, and cerebrospinal fluid metabolomes in children with b-cell acute lymphoblastic leukemia
title_full_unstemmed Comparison of the blood, bone marrow, and cerebrospinal fluid metabolomes in children with b-cell acute lymphoblastic leukemia
title_short Comparison of the blood, bone marrow, and cerebrospinal fluid metabolomes in children with b-cell acute lymphoblastic leukemia
title_sort comparison of the blood bone marrow and cerebrospinal fluid metabolomes in children with b cell acute lymphoblastic leukemia
url https://doi.org/10.1038/s41598-021-99147-6
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