Summary of study ST000157

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.

See: https://www.metabolomicsworkbench.org/about/howtocite.php

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Study IDST000157
Study Title13C mass isotopomer analysis (LCMS flux studies) MLL-AF9 (part II)
Study Typetimecourse
Study SummaryHow 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.
Institute
University of Michigan
DepartmentMolecular and Human genetics (Baylor College of Medicine)
LaboratoryNakada Lab
Last NameSaitoh
First NameYusuke
AddressHouston, TX
Emailaraskind@med.umich.edu
Phone713-798-1175
Submit Date2015-01-13
Num Groups2
Total Subjects18
Raw Data AvailableYes
Raw Data File Type(s).xml, .bin, .cd, .cg
Analysis Type DetailLC-MS
Release Date2016-01-13
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:SU000301
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 Cell type Labeling time, min 1,2-13C2-labeled glucose concentration, g/L
SA012294S00017000AMPKαfl/fl 5 0.2
SA012295S00016998AMPKαfl/fl 5 0.2
SA012296S00016994AMPKαfl/fl 5 0.2
SA012297S00016996AMPKαfl/fl 5 0.2
SA012298S00016990AMPKαfl/fl 5 2
SA012299S00016992AMPKαfl/fl 5 2
SA012300S00016999AMPKαfl/fl 60 0.2
SA012301S00016995AMPKαfl/fl 60 0.2
SA012302S00017001AMPKαfl/fl 60 0.2
SA012303S00016997AMPKαfl/fl 60 0.2
SA012304S00016991AMPKαfl/fl 60 2
SA012305S00016993AMPKαfl/fl 60 2
SA012288S00017006AMPKαΔ/Δ 5 0.2
SA012289S00017002AMPKαΔ/Δ 5 0.2
SA012290S00017004AMPKαΔ/Δ 5 0.2
SA012291S00017003AMPKαΔ/Δ 60 0.2
SA012292S00017005AMPKαΔ/Δ 60 0.2
SA012293S00017007AMPKαΔ/Δ 60 0.2
Showing results 1 to 18 of 18

Collection:

Collection ID:CO000295
Sample Type:Cells

Treatment:

Treatment ID:TR000315

Sample Preparation:

Sampleprep ID:SP000309
Sampleprep Protocol Filename:Gly-TCA-nucleotides_analysis_protocol-2015-03-09.docx

Combined analysis:

Analysis ID AN000448
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

Chromatography:

Chromatography ID:CH000319
Methods ID:AQM020
Methods Filename:QTOF-002-HILIC-35min-1mm.m
Instrument Name:Agilent 1260
Column Name:Phenomenex Luna NH2 (150 x 1mm, 3um)
Chromatography Type:HILIC

MS:

MS ID:MS000389
Analysis ID:AN000448
Instrument Name:Agilent 6520 QTOF
Instrument Type:QTOF
MS Type:ESI
Ion Mode:NEGATIVE
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