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
| Study ID | ST000157 |
| Study Title | 13C mass isotopomer analysis (LCMS flux studies) MLL-AF9 (part II) |
| Study Type | timecourse |
| 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. |
| Institute | University of Michigan |
| Department | Molecular and Human genetics (Baylor College of Medicine) |
| Laboratory | Nakada Lab |
| Last Name | Saitoh |
| First Name | Yusuke |
| Address | Houston, TX |
| araskind@med.umich.edu | |
| Phone | 713-798-1175 |
| Submit Date | 2015-01-13 |
| Num Groups | 2 |
| Total Subjects | 18 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | d |
| Analysis Type Detail | LC-MS |
| Release Date | 2016-01-13 |
| Release Version | 1 |
Select appropriate tab below to view additional metadata details:
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 |
|---|---|---|---|---|
| SA012294 | S00017000 | AMPKαfl/fl | 5 | 0.2 |
| SA012295 | S00016998 | AMPKαfl/fl | 5 | 0.2 |
| SA012296 | S00016994 | AMPKαfl/fl | 5 | 0.2 |
| SA012297 | S00016996 | AMPKαfl/fl | 5 | 0.2 |
| SA012298 | S00016990 | AMPKαfl/fl | 5 | 2 |
| SA012299 | S00016992 | AMPKαfl/fl | 5 | 2 |
| SA012300 | S00016999 | AMPKαfl/fl | 60 | 0.2 |
| SA012301 | S00016995 | AMPKαfl/fl | 60 | 0.2 |
| SA012302 | S00017001 | AMPKαfl/fl | 60 | 0.2 |
| SA012303 | S00016997 | AMPKαfl/fl | 60 | 0.2 |
| SA012304 | S00016991 | AMPKαfl/fl | 60 | 2 |
| SA012305 | S00016993 | AMPKαfl/fl | 60 | 2 |
| SA012288 | S00017006 | AMPKαΔ/Δ | 5 | 0.2 |
| SA012289 | S00017002 | AMPKαΔ/Δ | 5 | 0.2 |
| SA012290 | S00017004 | AMPKαΔ/Δ | 5 | 0.2 |
| SA012291 | S00017003 | AMPKαΔ/Δ | 60 | 0.2 |
| SA012292 | S00017005 | AMPKαΔ/Δ | 60 | 0.2 |
| SA012293 | S00017007 | AMPKαΔ/Δ | 60 | 0.2 |
| Showing results 1 to 18 of 18 |
Collection:
| Collection ID: | CO000295 |
| Collection Summary: | - |
| Sample Type: | Cells |
Treatment:
| Treatment ID: | TR000315 |
Sample Preparation:
| Sampleprep ID: | SP000309 |
| Sampleprep Summary: | - |
| 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 |
| Acquisition Parameters File: | QTOF-002-HILIC-35min-1mm.m |
| Processing Parameters File: | EX00388-Flux-Quant-method.m |
