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

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 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)d
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

Select appropriate tab below to view additional metadata details:


Collection:

Collection ID:CO000295
Collection Summary:-
Sample Type:Cells
  logo