Summary of project PR002390
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
| 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 |
Summary of all studies in project PR002390
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST003819 | Polar metabolite profiling of SLC31A1 knockout cells compared to intergenic sgRNA containing cells | Homo sapiens | Boston Childrens Hospital | MS | 2025-12-22 | 1 | 24 | Uploaded data (1.4G)* |
| ST003820 | Polar metabolite profiling of SLC31A1 knockout cells with or without rescue with over-expression of SLC31A1, and control intergenic cells | Homo sapiens | Boston Childrens Hospital | MS | 2025-12-22 | 1 | 12 | Uploaded data (1.3G)* |
| ST003821 | Polar metabolite profiling of BCS-treated SEM cells with or without rescue with copper (ii) chloride | Homo sapiens | Boston Childrens Hospital | MS | 2025-12-22 | 1 | 12 | Uploaded data (1.6G)* |
| ST003822 | Polar metabolite profiling of SLC31A1 knockout or control cells with or without rescue with over-expression of AOX | Homo sapiens | Boston Childrens Hospital | MS | 2025-12-22 | 1 | 18 | Uploaded data (2G)* |
| ST003823 | Polar metabolite profiling of BCS-treated SEM cells with or without genetic overexpression of AOX. | Homo sapiens | Boston Childrens Hospital | MS | 2025-12-22 | 1 | 12 | Uploaded data (1.4G)* |
| ST003824 | Polar metabolite profiling of BCS-treated SEM cells with or without pyruvate and uridine supplementation | Homo sapiens | Boston Childrens Hospital | MS | 2025-12-22 | 1 | 12 | Uploaded data (1.4G)* |
| ST003825 | Polar metabolite profiling of SLC31A1 knockout or control cells with or without pyruvate and uridine treatment | Homo sapiens | Boston Childrens Hospital | MS | 2025-12-22 | 1 | 12 | Uploaded data (1.3G)* |
| ST003826 | Polar metabolite profiling of TTM-treated SEM cells | Homo sapiens | Boston Childrens Hospital | MS | 2025-12-22 | 1 | 12 | Uploaded data (1.7G)* |
| ST003827 | Polar metabolite profiling of mouse cerebrospinal fluid (CSF) from control mice and mice with leukemia in the central nervous system (CNS) | Mus musculus | Boston Childrens Hospital | MS | 2025-12-22 | 1 | 9 | Uploaded data (1G)* |
| ST003831 | Folate profiling of human CSF from pediatric ALL patients | Homo sapiens | Boston Childrens Hospital | MS | 2025-12-22 | 1 | 285 | Uploaded data (17G)* |
| ST003832 | Polar metabolite profiling of BCS-treated SEM cells with or without rescue with copper (ii) chloride and 15N-amide-glutamine tracing | Homo sapiens | Boston Childrens Hospital | MS | 2025-12-22 | 1 | 18 | Uploaded data (2G)* |
| ST003838 | Polar metabolite profiling of human CSF from pediatric ALL patients | Homo sapiens | Boston Childrens Hospital | MS | 2025-12-22 | 1 | 285 | Uploaded data (29.4G)* |
| ST004416 | Polar metabolite profiling of BCS-treated SEM cells with or without inosine and uridine supplementation | Homo sapiens | Boston Childrens Hospital | MS | 2025-12-22 | 1 | 24 | Uploaded data (2.5G)* |
| ST004417 | Polar metabolite profiling of NALM6, REH, or MOLT16 cells treated with BCS or copper chloride. | Homo sapiens | Boston Childrens Hospital | MS | 2025-12-22 | 1 | 27 | Uploaded data (3.4G)* |
| ST004418 | Polar metabolite profiling of BCS-treated NALM6, REH or MOLT16 cells with or without rescue with copper (II) chloride and 15N-amide-glutamine tracing | Homo sapiens | Boston Children's Hospital | MS | 2025-12-22 | 1 | 27 | Uploaded data (3.4G)* |
| ST004463 | Polar metabolite profiling of SEM or NALM6 cells treated with BCS, 6-MP, MTX, ADDA 5, or a combination, with concurrent 15N-amide-glutamine tracing | Homo sapiens | Boston Childrens Hospital | MS | 2025-12-22 | 1 | 42 | Uploaded data (5.3G)* |
| ST004464 | Polar metabolite profiling of SEM-luciferase cells purified from the skulls and spleens of mice on copper replete diet (CuR+vehicle) or copper depleted diet with zinc acetate drinking water (CuD+ZnAc) and pulsed with 3-13C serine tracer. | Mus musculus | Boston Childrens Hospital | MS | 2025-12-22 | 1 | 24 | Uploaded data (2.5G)* |
| ST004468 | Polar metabolite profiling of SEM or NALM6 cells treated with BCS, 6-MP, MTX, ADDA 5, or a combination. | Homo sapiens | Boston Childrens Hospital | MS | 2025-12-22 | 1 | 42 | Uploaded data (4.5G)* |
