Summary of Study ST003838

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR002390. The data can be accessed directly via it's Project DOI: 10.21228/M8Q250 This work is supported by NIH grant, U2C- DK119886. See: https://www.metabolomicsworkbench.org/about/howtocite.php

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Study IDST003838
Study TitlePolar metabolite profiling of human CSF from pediatric ALL patients
Study SummaryTo investigate the changes in CSF metabolites in human pediatric acute lymphoblastic leukemia (ALL) patients, human CSF from pediatric ALL patients was collected at 5 standardized time points as part of the DFCI 16-001 trial and subjected to non-polar and polar metabolomics. Targetted analysis of polar metabolites in these CSF samples revealed expected changes in asparagine, consistent with the effects of pegylated asparaginase treatment. Untargeted analysis using Compound Discoverer revealed changes in nucleotides and modified nucleotides between F0 and F1 timepoint.
Institute
Boston Childrens Hospital
Last NameWong
First NameAlan
Address300 Longwood Avenue
Emailalan.wong@childrens.harvard.edu
Phone(617) 355-7433
Submit Date2025-03-26
Num Groups4
Raw Data AvailableYes
Raw Data File Type(s)mzML, raw(Thermo)
Analysis Type DetailLC-MS
Release Date2025-12-22
Release Version1
Alan Wong Alan Wong
https://dx.doi.org/10.21228/M8Q250
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Project:

Project ID:PR002390
Project DOI:doi: 10.21228/M8Q250
Project Title:In vivo CRISPR screen identifies copper metabolism as a vulnerability in acute lymphoblastic leukemia
Project Summary:The nutrient-sparse cerebrospinal fluid (CSF) poses a significant challenge to spreading cancer cells. Despite this challenge, leukemia often spreads to the CSF and represents a significant clinical complication. To uncover nutritional dependencies of leukemia cells in the CSF that could be targeted therapeutically, we conducted an in vivo targeted CRISPR screen in a xenograft model of leukemia. We found that SLC31A1, the primary cell surface copper importer, is a genetic dependency of leukemia in both the central nervous system as well as in the hematopoietic organs. Perturbation of copper metabolism leads to complex IV deficiency, perturbed nucleotide metabolism and slowed leukemia cell proliferation. Furthermore, nutritional copper depletion reduced cancer progression in cell line based and patient-derived xenograft models of leukemia. Copper thus appears to be an actionable micronutrient in leukemia.
Institute:Boston Children's Hospital
Department:Pathology
Laboratory:Naama Kanarek
Last Name:Wong
First Name:Alan
Address:300 Longwood Avenue, Boston, MA, 02115, USA
Email:alan.wong@childrens.harvard.edu
Phone:(617) 355-7433
Funding Source:NCI 1R01CA282477-01A1

Subject:

Subject ID:SU004655
Subject Type:Mammal
Subject Species:Homo sapiens
Taxonomy ID:9606
Gender:Male and female

Factors:

Subject type: Mammal; Subject species: Homo sapiens (Factor headings shown in green)

mb_sample_id local_sample_id Sample source Timepoint
SA532849AYW210Human CSF F0
SA532850AYW259Human CSF F0
SA532851AYW254Human CSF F0
SA532852AYW249Human CSF F0
SA532853AYW244Human CSF F0
SA532854AYW239Human CSF F0
SA532855AYW234Human CSF F0
SA532856AYW225Human CSF F0
SA532857AYW220Human CSF F0
SA532858AYW215Human CSF F0
SA532859AYW205Human CSF F0
SA532860AYW269Human CSF F0
SA532861AYW200Human CSF F0
SA532862AYW190Human CSF F0
SA532863AYW185Human CSF F0
SA532864AYW180Human CSF F0
SA532865AYW175Human CSF F0
SA532866AYW170Human CSF F0
SA532867NK571Human CSF F0
SA532868NK566Human CSF F0
SA532869NK561Human CSF F0
SA532870AYW264Human CSF F0
SA532871AYW274Human CSF F0
SA532872NK551Human CSF F0
SA532873AYW347Human CSF F0
SA532874AYW392Human CSF F0
SA532875AYW387Human CSF F0
SA532876AYW382Human CSF F0
SA532877AYW377Human CSF F0
SA532878AYW372Human CSF F0
SA532879AYW367Human CSF F0
SA532880AYW362Human CSF F0
SA532881AYW357Human CSF F0
SA532882AYW352Human CSF F0
SA532883AYW338Human CSF F0
SA532884AYW279Human CSF F0
SA532885AYW333Human CSF F0
SA532886AYW328Human CSF F0
SA532887AYW323Human CSF F0
SA532888AYW318Human CSF F0
SA532889AYW313Human CSF F0
SA532890AYW308Human CSF F0
SA532891AYW303Human CSF F0
SA532892AYW298Human CSF F0
SA532893AYW289Human CSF F0
SA532894AYW284Human CSF F0
SA532895NK556Human CSF F0
SA532896NK496Human CSF F0
SA532897NK521Human CSF F0
SA532898NK506Human CSF F0
SA532899NK501Human CSF F0
SA532900NK511Human CSF F0
SA532901NK536Human CSF F0
SA532902NK546Human CSF F0
SA532903NK541Human CSF F0
SA532904NK516Human CSF F0
SA532905NK531Human CSF F0
SA532906AYW348Human CSF F1
SA532907AYW260Human CSF F1
SA532908AYW186Human CSF F1
SA532909AYW240Human CSF F1
SA532910NK502Human CSF F1
SA532911AYW339Human CSF F1
SA532912AYW235Human CSF F1
SA532913AYW324Human CSF F1
SA532914AYW191Human CSF F1
SA532915AYW368Human CSF F1
SA532916AYW265Human CSF F1
SA532917NK522Human CSF F1
SA532918AYW201Human CSF F1
SA532919AYW363Human CSF F1
SA532920AYW329Human CSF F1
SA532921AYW206Human CSF F1
SA532922AYW245Human CSF F1
SA532923NK537Human CSF F1
SA532924AYW211Human CSF F1
SA532925AYW255Human CSF F1
SA532926AYW373Human CSF F1
SA532927AYW216Human CSF F1
SA532928AYW334Human CSF F1
SA532929AYW250Human CSF F1
SA532930AYW353Human CSF F1
SA532931AYW304Human CSF F1
SA532932NK507Human CSF F1
SA532933NK497Human CSF F1
SA532934AYW226Human CSF F1
SA532935AYW358Human CSF F1
SA532936AYW221Human CSF F1
SA532937AYW270Human CSF F1
SA532938AYW280Human CSF F1
SA532939NK552Human CSF F1
SA532940AYW299Human CSF F1
SA532941NK557Human CSF F1
SA532942AYW290Human CSF F1
SA532943AYW393Human CSF F1
SA532944NK517Human CSF F1
SA532945NK547Human CSF F1
SA532946NK562Human CSF F1
SA532947AYW309Human CSF F1
SA532948NK567Human CSF F1
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Collection:

Collection ID:CO004648
Collection Summary:Excess human CSF during planned lumbar punctures was collected and kept on ice. Human CSF was aliquoted and stored at -80C. Samples were thawed once and re-aliquoted into 20uL aliquots and refrozen at -80C.
Sample Type:Cerebrospinal fluid

Treatment:

Treatment ID:TR004664
Treatment Summary:Human CSF samples were collected from patients enrolled in the DFCI 16-001 trial. Briefly, the lumbar puncture timepoints from which CSF was collected were as follows: F0 = lumbar puncture from the day of diagnosis (LP), F1 = day 18 of induction LP (induction is the phase in which intensive systemic and intrathecal chemotherapy is given to induce remission and kill most cancer cells. If successful, the patient proceeds to the first consolidation phase (Consolidation 1A) in which additional therapy is given to eradicate residual disease), F2 = central nervous system (CNS) phase LP 1 - (the 3-week CNS phase of therapy follows Consolidation 1A, and consists of therapy directed to the CNS through intrathecal administration. This helps to kill any cancer cells that are in the CNS, and to prevent subsequent spread of cancer into the CNS). This first LP is at the beginning of the CNS phase. F3 = CNS Phase LP 4 - this is the last LP during the CNS phase, F4 = 1st LP of Consolidation II - this phase follows the CNS phase and consists of additional therapy to ensure durable remission

Sample Preparation:

Sampleprep ID:SP004661
Sampleprep Summary:Each sample contained 20uL of human CSF. 160uL of 100% LC-MS grade methanol supplemented with isotopically-labelled amino acid standards [Cambridge Isotope Laboratories, MSK-A2-1.2], aminopterin, and reduced glutathione standard [Cambridge Isotope Laboratories, CNLM-6245-10]). with repeated pipetting up and down and vortexing for 10 seconds. Then, 40uL of LCMS-grade water containing 125 mM Ammonium Acetate, 10 mM Na-Ascorbate, and 7.9 mg/mL 5,5-dithio-bis-(2-nitrobenzoic acid (Ellman's reagent) was added, and the sample vortexex for another 10 seconds. Samples were then centrifuged for 10 minutes at 18,000 g to pellet debris. The supernatant was transferred to a new tube and dried on ice using a liquid nitrogen dryer and stored at -80C. The dried metabolites were then resuspended in 15uL and 2uL was injected.

Combined analysis:

Analysis ID AN007508 AN007509 AN007510
Chromatography ID CH005697 CH005697 CH005697
MS ID MS007205 MS007206 MS007207
Analysis type MS MS MS
Chromatography type HILIC HILIC HILIC
Chromatography system Thermo Vanquish Thermo Vanquish Thermo Vanquish
Column SeQuant ZIC-HILIC (150 x 2.1mm,5um) SeQuant ZIC-HILIC (150 x 2.1mm,5um) SeQuant ZIC-HILIC (150 x 2.1mm,5um)
MS Type ESI ESI ESI
MS instrument type Orbitrap Orbitrap Orbitrap
MS instrument name Thermo Q Exactive Orbitrap Thermo Q Exactive Orbitrap Thermo Q Exactive Orbitrap
Ion Mode UNSPECIFIED POSITIVE NEGATIVE
Units Normalized peak area Normalized peak area Normalized peak area

Chromatography:

Chromatography ID:CH005697
Chromatography Summary:2 μL of each sample was injected into a ZIC-pHILIC 150 x 2.1 mm (5 μm particle size) column (EMD Millipore) operated on a Vanquish™ Flex UHPLC system (Thermo Fisher Scientific). Chromatographic separation was achieved using the following conditions: buffer A was acetonitrile; buffer B was 20 mM ammonium carbonate, 0.1% ammonium hydroxide in water; resulting pH is around 9 without pH adjustment. Gradient conditions used were: 0-20 min: linear gradient from 20% to 80% B; 20-24 min: hold at 80% B; 24-24.1 min: from 80% to 20% B; 24.1-32 min: hold at 20% B at 0.150 mL/min flow rate. The column oven and autosampler tray were held at 25 °C and 4 °C, respectively.
Instrument Name:Thermo Vanquish
Column Name:SeQuant ZIC-HILIC (150 x 2.1mm,5um)
Column Temperature:25
Flow Gradient:Gradient conditions were as follows: linear gradient from 20 to 80% B; 20–20.5 min: from 80 to 20% B; 20.5–28 min: hold at 20% B.
Flow Rate:0.15 mL/min
Solvent A:100% acetonitrile
Solvent B:100% water; 20mM ammonium carbonate; 0.1% ammonium hydroxide
Chromatography Type:HILIC

MS:

MS ID:MS007205
Analysis ID:AN007508
Instrument Name:Thermo Q Exactive Orbitrap
Instrument Type:Orbitrap
MS Type:ESI
MS Comments:MS data acquisition was performed using a QExactive benchtop orbitrap mass spectrometer equipped with an Ion Max source and a HESI II probe (Thermo Fisher Scientific) and polarity switching was used. Four scans were used: full scans in both positive and negative ionization mode in a range of m/z = 70–1000, with the resolution set at 70,000, the AGC target at 1 × 106, and the maximum injection time (Max IT) at 20 msec from 0-20 minutes. A third scan in the negative mode was used with range of m/z = 220-700 from 0-20 minutes and the same resolution, AGC settings with 30ms Max IT. Lastly, a targeted-SIM scan was added with a resolution of 35k, AGC target 1e5, and max IT 20ms, isolation window = 1.0 m/z, with an inclusion m/z of 503.0552 (corresponding to Ellman-derivatized glutathione). Tune file parameters were: spray voltage = 3.5kV, capillary temperature = 320C, S-lens RF = 50, auxillary gas temperature = 350C. Data was analyzed by targeted metabolomics approaches (using TraceFinder and matching to an in-house library of standards), as well as untargeted approaches (by CompoundDiscoverer).
Ion Mode:UNSPECIFIED
  
MS ID:MS007206
Analysis ID:AN007509
Instrument Name:Thermo Q Exactive Orbitrap
Instrument Type:Orbitrap
MS Type:ESI
MS Comments:MS data acquisition was performed using a QExactive benchtop orbitrap mass spectrometer equipped with an Ion Max source and a HESI II probe (Thermo Fisher Scientific) and polarity switching was used. Four scans were used: full scans in both positive and negative ionization mode in a range of m/z = 70–1000, with the resolution set at 70,000, the AGC target at 1 × 106, and the maximum injection time (Max IT) at 20 msec from 0-20 minutes. A third scan in the negative mode was used with range of m/z = 220-700 from 0-20 minutes and the same resolution, AGC settings with 30ms Max IT. Lastly, a targeted-SIM scan was added with a resolution of 35k, AGC target 1e5, and max IT 20ms, isolation window = 1.0 m/z, with an inclusion m/z of 503.0552 (corresponding to Ellman-derivatized glutathione). Tune file parameters were: spray voltage = 3.5kV, capillary temperature = 320C, S-lens RF = 50, auxillary gas temperature = 350C. Data was analyzed by targeted metabolomics approaches (using TraceFinder and matching to an in-house library of standards), as well as untargeted approaches (by CompoundDiscoverer).
Ion Mode:POSITIVE
  
MS ID:MS007207
Analysis ID:AN007510
Instrument Name:Thermo Q Exactive Orbitrap
Instrument Type:Orbitrap
MS Type:ESI
MS Comments:MS data acquisition was performed using a QExactive benchtop orbitrap mass spectrometer equipped with an Ion Max source and a HESI II probe (Thermo Fisher Scientific) and polarity switching was used. Four scans were used: full scans in both positive and negative ionization mode in a range of m/z = 70–1000, with the resolution set at 70,000, the AGC target at 1 × 106, and the maximum injection time (Max IT) at 20 msec from 0-20 minutes. A third scan in the negative mode was used with range of m/z = 220-700 from 0-20 minutes and the same resolution, AGC settings with 30ms Max IT. Lastly, a targeted-SIM scan was added with a resolution of 35k, AGC target 1e5, and max IT 20ms, isolation window = 1.0 m/z, with an inclusion m/z of 503.0552 (corresponding to Ellman-derivatized glutathione). Tune file parameters were: spray voltage = 3.5kV, capillary temperature = 320C, S-lens RF = 50, auxillary gas temperature = 350C. Data was analyzed by targeted metabolomics approaches (using TraceFinder and matching to an in-house library of standards), as well as untargeted approaches (by CompoundDiscoverer).
Ion Mode:NEGATIVE
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