Summary of study ST000308

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 PR000223. The data can be accessed directly via it's Project DOI: 10.21228/M8PW2T This work is supported by NIH grant, U2C- DK119886.

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Study IDST000308
Study Title13C mass isotopomer analysis (LCMS flux studies) MLL-AF9 (part I)
Study Type1,2-13C2 Flux analysis
Study Summary"How cancer cells adapt to metabolically adverse conditions in patients and strive to proliferate is a fundamental question in cancer biology. Here we show that AMP-activated protein kinase (AMPK), a metabolic checkpoint kinase, confers metabolic stress resistance to leukemia-initiating cells (LICs) and promotes leukemogenesis. Upon dietary restriction, MLL-AF9-induced murine acute myeloid leukemia (AML) activated AMPK and maintained leukemogenic potential. AMPK deletion significantly delayed leukemogenesis and depleted LICs by reducing the expression of glucose transporter 1 (Glut1), compromising glucose flux, and increasing oxidative stress and DNA damage. LICs were particularly dependent on AMPK to suppress oxidative stress in the hypoglycemic bone marrow environment. Strikingly, AMPK inhibition synergized with physiological metabolic stress caused by dietary restriction and profoundly suppressed leukemogenesis. Our results indicate that AMPK protects LICs from metabolic stress and that combining AMPK inhibition with physiological metabolic stress potently suppresses AML by inducing oxidative stress and DNA damage. Research is published: http://www.sciencedirect.com/science/article/pii/S1934590915003744 "
Institute
University of Michigan
DepartmentMolecular and Human genetics (Baylor College of Medicine)
LaboratoryNakada Lab (Baylor College of Medicine)
Last NameSaitoh
First NameYusuke
AddressHouston, TX
EmailYusuke.Saitoh@bcm.edu
Phone713-798-1175
Submit Date2015-06-12
Num Groups7
Total Subjects18
Study Comments1. Collect leukemia cells from MLL-AF9 leukemia mouse bone marrow. 2. Leukemia cell were cultured in RPMI1640 medium for 16hr. 3. Cell pellets were resuspend in pre-warmed labeling medium containing 1,2-13C2-glucose(2g/L) and incubated for 5min (sample 5) or 60min(sample 60).
Publicationshttp://www.sciencedirect.com/science/article/pii/S1934590915003744
Raw Data AvailableYes
Raw Data File Type(s).bin,.xsd,.cd,.cg,.xml
Analysis Type DetailLC-MS
Release Date2016-01-08
Release Version1
Yusuke Saitoh Yusuke Saitoh
https://dx.doi.org/10.21228/M8PW2T
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Project:

Project ID:PR000223
Project DOI:doi: 10.21228/M8PW2T
Project Title:Leukemia stem cells studies_dup
Project Type:Glycolysis/TCA/Nucleotide analysis (tissue/cells)
Project Summary:Define the function of AMPK metabolic sensor in leukemia stem cells
Institute:Baylor College of Medicine
Department:Molecular and Human genetics
Laboratory:Nakada Lab
Last Name:Nakada
First Name:Daisuke
Address:Houston, TX
Email:nakada@bcm.edu
Phone:713-798-1175

Subject:

Subject ID:SU000328
Subject Type:Animal
Subject Species:Mus musculus
Taxonomy ID:10090
Species Group:Mammal

Factors:

Subject type: Animal; Subject species: Mus musculus (Factor headings shown in green)

mb_sample_id local_sample_id Timepoint Type Treatment
SA014017S000149410 KO yes
SA014018S000149380 KO yes
SA014019S000149350 KO yes
SA014020S000149260 WT no
SA014021S000149320 WT yes
SA014022S000149290 WT yes
SA014023S000149365 KO yes
SA014024S000149425 KO yes
SA014025S000149395 KO yes
SA014026S000149275 WT yes
SA014027S000149335 WT yes
SA014028S000149305 WT yes
SA014029S0001494360 KO yes
SA014030S0001493760 KO yes
SA014031S0001494060 KO yes
SA014032S0001493160 WT yes
SA014033S0001493460 WT yes
SA014034S0001492860 WT yes
Showing results 1 to 18 of 18

Collection:

Collection ID:CO000322
Collection Summary:None available, see publication
Sample Type:Cells

Treatment:

Treatment ID:TR000342
Treatment Summary:None, see publication

Sample Preparation:

Sampleprep ID:SP000336
Sampleprep Summary:See attached file.

Combined analysis:

Analysis ID AN000488
Analysis type MS
Chromatography type HILIC
Chromatography system Agilent 1260
Column Phenomenex Luna NH2 (150 x 1mm, 3um)
MS Type ESI
MS instrument type QTOF
MS instrument name Agilent 6520 QTOF
Ion Mode NEGATIVE
Units Area normalized

Chromatography:

Chromatography ID:CH000348
Instrument Name:Agilent 1260
Column Name:Phenomenex Luna NH2 (150 x 1mm, 3um)
Chromatography Type:HILIC

MS:

MS ID:MS000426
Analysis ID:AN000488
Instrument Name:Agilent 6520 QTOF
Instrument Type:QTOF
MS Type:ESI
Ion Mode:NEGATIVE
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