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.

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

Perform statistical analysis  |  Show all samples  |  Show named metabolites  |  Download named metabolite data  
Download mwTab file (text)   |  Download mwTab file(JSON)   |  Download data files (Contains raw data)
Study IDST000308
Study Title13C mass isotopomer analysis (LCMS flux studies) MLL-AF9 (part I)
Study Type1,2-13C2 Flux analysis
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. 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)d
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

Select appropriate tab below to view additional metadata details:


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

MS:

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