Summary of Study ST003831

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 IDST003831
Study TitleFolate 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 57 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. Analysis of folate species in these CSF samples revealed expected changes in 5-methyl tetrahydrofolate levels, consistent with the effects of methotrexate treatment.
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:SU004590
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
SA523425AYW210Human CSF F0
SA523426AYW259Human CSF F0
SA523427AYW254Human CSF F0
SA523428AYW249Human CSF F0
SA523429AYW244Human CSF F0
SA523430AYW239Human CSF F0
SA523431AYW234Human CSF F0
SA523432AYW225Human CSF F0
SA523433AYW220Human CSF F0
SA523434AYW215Human CSF F0
SA523435AYW205Human CSF F0
SA523436AYW269Human CSF F0
SA523437AYW200Human CSF F0
SA523438AYW190Human CSF F0
SA523439AYW185Human CSF F0
SA523440AYW180Human CSF F0
SA523441AYW175Human CSF F0
SA523442AYW170Human CSF F0
SA523443NK571Human CSF F0
SA523444NK566Human CSF F0
SA523445NK561Human CSF F0
SA523446AYW264Human CSF F0
SA523447AYW274Human CSF F0
SA523448NK551Human CSF F0
SA523449AYW347Human CSF F0
SA523450AYW392Human CSF F0
SA523451AYW387Human CSF F0
SA523452AYW382Human CSF F0
SA523453AYW377Human CSF F0
SA523454AYW372Human CSF F0
SA523455AYW367Human CSF F0
SA523456AYW362Human CSF F0
SA523457AYW357Human CSF F0
SA523458AYW352Human CSF F0
SA523459AYW338Human CSF F0
SA523460AYW279Human CSF F0
SA523461AYW333Human CSF F0
SA523462AYW328Human CSF F0
SA523463AYW323Human CSF F0
SA523464AYW318Human CSF F0
SA523465AYW313Human CSF F0
SA523466AYW308Human CSF F0
SA523467AYW303Human CSF F0
SA523468AYW298Human CSF F0
SA523469AYW289Human CSF F0
SA523470AYW284Human CSF F0
SA523471NK556Human CSF F0
SA523472NK496Human CSF F0
SA523473NK521Human CSF F0
SA523474NK506Human CSF F0
SA523475NK501Human CSF F0
SA523476NK511Human CSF F0
SA523477NK536Human CSF F0
SA523478NK546Human CSF F0
SA523479NK541Human CSF F0
SA523480NK516Human CSF F0
SA523481NK531Human CSF F0
SA523482AYW348Human CSF F1
SA523483AYW260Human CSF F1
SA523484AYW186Human CSF F1
SA523485AYW240Human CSF F1
SA523486NK502Human CSF F1
SA523487AYW339Human CSF F1
SA523488AYW235Human CSF F1
SA523489AYW324Human CSF F1
SA523490AYW191Human CSF F1
SA523491AYW368Human CSF F1
SA523492AYW265Human CSF F1
SA523493NK522Human CSF F1
SA523494AYW201Human CSF F1
SA523495AYW363Human CSF F1
SA523496AYW329Human CSF F1
SA523497AYW206Human CSF F1
SA523498AYW245Human CSF F1
SA523499NK537Human CSF F1
SA523500AYW211Human CSF F1
SA523501AYW255Human CSF F1
SA523502AYW373Human CSF F1
SA523503AYW216Human CSF F1
SA523504AYW334Human CSF F1
SA523505AYW250Human CSF F1
SA523506AYW353Human CSF F1
SA523507AYW304Human CSF F1
SA523508NK507Human CSF F1
SA523509NK497Human CSF F1
SA523510AYW226Human CSF F1
SA523511AYW358Human CSF F1
SA523512AYW221Human CSF F1
SA523513AYW270Human CSF F1
SA523514AYW280Human CSF F1
SA523515NK552Human CSF F1
SA523516AYW299Human CSF F1
SA523517NK557Human CSF F1
SA523518AYW290Human CSF F1
SA523519AYW393Human CSF F1
SA523520NK517Human CSF F1
SA523521NK547Human CSF F1
SA523522NK562Human CSF F1
SA523523AYW309Human CSF F1
SA523524NK567Human CSF F1
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Collection:

Collection ID:CO004583
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:TR004599
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:SP004596
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 10uL was injected.

Combined analysis:

Analysis ID AN007410
Chromatography ID CH005614
MS ID MS007102
Analysis type MS
Chromatography type Reversed phase
Chromatography system Thermo Vanquish
Column Merck Supelco Ascentis Express C18 (150 x 2.1mm,2.7um)
MS Type ESI
MS instrument type Orbitrap
MS instrument name Thermo Q Exactive Orbitrap
Ion Mode POSITIVE
Units Normalized peak area

Chromatography:

Chromatography ID:CH005614
Chromatography Summary:5 μl was injected onto a Ascentis Express C18 HPLC column (2.7 μm × 15 cm × 2.1 mm; Sigma Aldrich). The column oven and autosampler tray were held at 30 °C and 4 °C, respectively. The following conditions were used to achieve chromatographic separation: buffer A was 0.1% formic acid in water; buffer B was acetonitrile with 0.1% formic acid. The chromatographic gradient was run at a flow rate of 0.250 ml min−1 as follows: 0–5 min: gradient was held at 5% B; 5–10 min: linear gradient of 5% to 36% B; 10.1–14.0 min: linear gradient from 36–95% B; 14.1–18.0 min: gradient was returned to 5% B.
Instrument Name:Thermo Vanquish
Column Name:Merck Supelco Ascentis Express C18 (150 x 2.1mm,2.7um)
Column Temperature:30
Flow Gradient:0–5 min: gradient was held at 5% B; 5–10 min: linear gradient from 5% to 36% B; 10.1–14.0 min: linear gradient from 36–95% B; 14.1–18.0 min: gradient was returned to 5% B.
Flow Rate:0.25 mL/min
Solvent A:100% water; 0.1% formic acid
Solvent B:100% acetonitrile; 0.1% formic acid
Chromatography Type:Reversed phase

MS:

MS ID:MS007102
Analysis ID:AN007410
Instrument Name:Thermo Q Exactive Orbitrap
Instrument Type:Orbitrap
MS Type:ESI
MS Comments:The mass spectrometer was operated in full-scan, positive ionization mode using three narrow-range scans: 438–450 m/z; 452–462 m/z; and 470–478 m/z, with the resolution set at 70,000, the AGC target at 10e6, and the maximum injection time of 150 ms. HESI settings were: sheath gas flow rate: 40; Aux gas flow rate: 10; Sweep gas: 0; Spray voltage: 2.8 (neg) 3.5 (pos); Capillary temperature 300; S-lens RF level 50; Aux gas heater temp: 350.
Ion Mode:POSITIVE
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