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

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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:

Alternative Title:

Cell

Personal Author:

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

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.

Subject:

[+]

Pubmed ID:

26095251

Pubmed Central ID:

PMC4508757

Document Type:

Journal Article

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 ; ... More ▼

Collection(s):

CDC Public Access

Main Document Checksum:

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