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
| Study ID | ST000308 |
| Study Title | 13C mass isotopomer analysis (LCMS flux studies) MLL-AF9 (part I) |
| Study Type | 1,2-13C2 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 |
| Department | Molecular and Human genetics (Baylor College of Medicine) |
| Laboratory | Nakada Lab (Baylor College of Medicine) |
| Last Name | Saitoh |
| First Name | Yusuke |
| Address | Houston, TX |
| Yusuke.Saitoh@bcm.edu | |
| Phone | 713-798-1175 |
| Submit Date | 2015-06-12 |
| Num Groups | 7 |
| Total Subjects | 18 |
| Study Comments | 1. 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). |
| Publications | http://www.sciencedirect.com/science/article/pii/S1934590915003744 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | d |
| Analysis Type Detail | LC-MS |
| Release Date | 2016-01-08 |
| Release Version | 1 |
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 |
