Data-driven phenotypic dissection of AML reveals progenitor-like cells that correlate with prognosis

Levine, Jacob H.; Simonds, Erin F.; Bendall, Sean C.; Davis, Kara L.; Amir, El-ad D.; Tadmor, Michelle; Litvin, Oren; Fienberg, Harris; Jager, Astraea; Zunder, Eli; Finck, Rachel; Gedman, Amanda L.; Radtke, Ina; Downing, James R.; Pe’er, Dana; Nolan, Garry P.

doi:10.1016/j.cell.2015.05.047

Back to Previous Page

- Add this to...
- Twitter
- Facebook
- Google Bookmarks
- LinkedIn

Data-driven phenotypic dissection of AML reveals progenitor-like cells that correlate with prognosis

Published Date:

Jun 18 2015

Publisher's site:

http://dx.doi.org/10.1016/j.cell.2015.05.047 New Site Icon

Source:

Cell. 2015; 162(1):184-197.

[PDF - 4.17 MB]

Details:

Personal Authors:

Levine, Jacob H. ; Simonds, Erin F. ; Bendall, Sean C. ; Davis, Kara L. ; Amir, El-ad D. ; ... More ▼

Keywords:

[+]

Pubmed ID:

26095251

Pubmed Central ID:

PMC4508757

Description:

Acute myeloid leukemia (AML) manifests as phenotypically and functionally diverse cells, often within the same patient. Intratumor phenotypic and functional heterogeneity have been linked primarily by physical sorting experiments, which assume that functionally distinct subpopulations can be prospectively isolated by surface phenotypes. This assumption has proven problematic, and we therefore developed a data-driven approach. Using mass cytometry, we profiled surface and intracellular signaling proteins simultaneously in millions of healthy and leukemic cells. We developed PhenoGraph, which algorithmically defines phenotypes in high-dimensional single-cell data. PhenoGraph revealed that the surface phenotypes of leukemic blasts do not necessarily reflect their intracellular state. Using hematopoietic progenitors, we defined a signaling-based measure of cellular phenotype, which led to isolation of a gene expression signature that was predictive of survival in independent cohorts. This study presents new methods for large-scale analysis of single-cell heterogeneity and demonstrates their utility, yielding insights into AML pathophysiology.

Document Type:

Journal Article

Collection(s):

CDC Public Access

Funding:

1R00-GM104148/GM/NIGMS NIH HHS/United States
1R01CA130826/CA/NCI NIH HHS/United States
5U54CA143907/CA/NCI NIH HHS/United States
DP1 HD084071/HD/NICHD NIH HHS/United States
DP1-HD084071/DP/NCCDPHP CDC HHS/United States
DP2 OD002414/OD/NIH HHS/United States
DP2-OD002414/OD/NIH HHS/United States
HHSF223201210194C/PHS HHS/United States
HHSN272200700038C/PHS HHS/United States
N01-HV-00242/HV/NHLBI NIH HHS/United States
P01 CA034233/CA/NCI NIH HHS/United States
R00 GM104148/GM/NIGMS NIH HHS/United States
R01 CA164729/CA/NCI NIH HHS/United States
R01-CA164729/CA/NCI NIH HHS/United States
T32 AI007328/AI/NIAID NIH HHS/United States
T32 GM008798/GM/NIGMS NIH HHS/United States
U19 AI057229/AI/NIAID NIH HHS/United States
U19 AI057229/AI/NIAID NIH HHS/United States
U54-CA121852/CA/NCI NIH HHS/United States
U54CA149145/CA/NCI NIH HHS/United States

Supporting Files:

NIHMS705075-supplement-01.pdf	application/pdf
NIHMS705075-supplement-1.png	image/png
NIHMS705075-supplement-2.png	image/png
NIHMS705075-supplement-3.png	image/png
NIHMS705075-supplement-4.png	image/png
NIHMS705075-supplement-5.png	image/png
NIHMS705075-supplement-6.png	image/png
NIHMS705075-supplement-7.xlsx	application/vnd.openxmlformats-officedocument.spreadsheetml.sheet
NIHMS705075-supplement-8.xlsx	application/vnd.openxmlformats-officedocument.spreadsheetml.sheet
NIHMS705075-supplement-9.xlsx	application/vnd.openxmlformats-officedocument.spreadsheetml.sheet
nihms705075.nxml	application/octet-stream
nihms705075f1.gif	image/gif
nihms705075f1.jpg	image/jpeg
nihms705075f2.gif	image/gif
nihms705075f2.jpg	image/jpeg
nihms705075f3.gif	image/gif
nihms705075f3.jpg	image/jpeg
nihms705075f4.gif	image/gif
nihms705075f4.jpg	image/jpeg
nihms705075f5.gif	image/gif
nihms705075f5.jpg	image/jpeg
nihms705075f6.gif	image/gif
nihms705075f6.jpg	image/jpeg
nihms705075f7.gif	image/gif
nihms705075f7.jpg	image/jpeg

No Related Documents.

You May Also Like:

Phenotypic, genomic, and transcriptional characterization of Streptococcus pneumoniae interacting with human pharyngeal cells

Personal Author:

Kimaro Mlacha, Sheila Z; Romero-Steiner, Sandra; Dunning Hotopp, Julie C; Kumar, Nikhil; Ishmael, Nadeeza; Riley, David R; Farooq, Umar; Creasy, Todd H; Tallon, Luke J; Liu, Xinyue; Goldsmith, Cynthia S; Sampson, Jacquelyn; Carlone, George M; Hollingshead, Susan K; Scott, J Anthony G; Tettelin, Hervé;

Published:

Jun 09 2013

Source:

BMC Genomics. 2013; 14:383.

Description:

Background : Streptococcus pneumoniae is a leading cause of childhood morbidity and mortality worldwide, despite the availability of effective pneumococcal vaccines. Understanding the molecular interactions between the bacterium and the host will con...

File Type:

[PDF - 3.18 MB]
Levels of intracellular phosphorylated tenofovir and emtricitabine correlate with natural substrate concentrations in peripheral blood mononuclear cells of persons prescribed daily oral Truvada™ for HIV pre-exposure prophylaxis

Personal Author:

Haaland, Richard E.; Holder, Angela; Pau, Chou-Pong; Swaims-Kohlmeier, Alison; Dawson, Carolyn; Smith, Dawn K.; Segolodi, Tebogo M.; Thigpen, Michael C.; Paxton, Lynn A.; Parsons, Teresa L.; Hendrix, Craig W.; Hart, Clyde E.;

Published:

Jul 01 2017

Source:

J Acquir Immune Defic Syndr. 75(3):e86-e88.

Public Access
Available on:

July 01, 2018
Induction of stem-like cells with malignant properties by chronic exposure of human lung epithelial cells to single-walled carbon nanotubes

Personal Author:

Luanpitpong, Sudjit; Wang, Liying; Castranova, Vincent; Rojanasakul, Yon;

Published:

May 11 2014

Source:

Part Fibre Toxicol. 2014; 11:22.

Description:

Background : Carbon nanotubes (CNT) hold great promise to create new and better products for commercial and biomedical applications, but their long-term adverse health effects are a major concern. The objective of this study was to address human lung...

File Type:

[PDF - 2.99 MB]
Does Numeracy Correlate with Measures of Health Literacy in the Emergency Department?

Personal Author:

Griffey, Richard T.; Melson, Andrew T.; Lin, Margaret J.; Carpenter, Christopher R.; Goodman, Melody S.; Kaphingst, Kimberly A.;

Published:

Feb 2014

Source:

Acad Emerg Med. 21(2):147-153.

Description:

Objectives : To quantify the correlation between general numeracy and health literacy in an emergency department (ED) setting. : Methods : This was a prospective cross-sectional convenience sample study of adult patients in an urban, academic ED with...

File Type:

[PDF - 168.82 KB]
Mollaret-like Cells in Patients with West Nile Virus Infection

Personal Author:

Procop, Gary W.; Yen-Lieberman, Belinda; Prayson, Richard A.; Gordon, Steve M.;

Published:

Apr 2004

Source:

Emerg Infect Dis. 10(4):753-754.

File Type:

[PDF - 36.32 KB]