MIT Libraries logoDSpace@MIT

MIT
View Item 
  • DSpace@MIT Home
  • MIT Open Access Articles
  • MIT Open Access Articles
  • View Item
  • DSpace@MIT Home
  • MIT Open Access Articles
  • MIT Open Access Articles
  • View Item
JavaScript is disabled for your browser. Some features of this site may not work without it.

Single-Cell RNA-Seq Reveals AML Hierarchies Relevant to Disease Progression and Immunity

Author(s)
van Galen, Peter; Hovestadt, Volker; Wadsworth II, Marc H.; Hughes, Travis K.; Griffin, Gabriel K.; Battaglia, Sofia; Verga, Julia A.; Stephansky, Jason; Pastika, Timothy J.; Lombardi Story, Jennifer; Pinkus, Geraldine S.; Pozdnyakova, Olga; Galinsky, Ilene; Stone, Richard M.; Graubert, Timothy A.; Shalek, Alex K.; Aster, Jon C.; Lane, Andrew A.; Bernstein, Bradley E.; ... Show more Show less
Thumbnail
DownloadAccepted version (3.524Mb)
Publisher with Creative Commons License

Publisher with Creative Commons License

Creative Commons Attribution

Terms of use
Creative Commons Attribution-NonCommercial-NoDerivs License http://creativecommons.org/licenses/by-nc-nd/4.0/
Metadata
Show full item record
Abstract
Acute myeloid leukemia (AML) is a heterogeneous disease that resides within a complex microenvironment, complicating efforts to understand how different cell types contribute to disease progression. We combined single-cell RNA sequencing and genotyping to profile 38,410 cells from 40 bone marrow aspirates, including 16 AML patients and five healthy donors. We then applied a machine learning classifier to distinguish a spectrum of malignant cell types whose abundances varied between patients and between subclones in the same tumor. Cell type compositions correlated with prototypic genetic lesions, including an association of FLT3-ITD with abundant progenitor-like cells. Primitive AML cells exhibited dysregulated transcriptional programs with co-expression of stemness and myeloid priming genes and had prognostic significance. Differentiated monocyte-like AML cells expressed diverse immunomodulatory genes and suppressed T cell activity in vitro. In conclusion, we provide single-cell technologies and an atlas of AML cell states, regulators, and markers with implications for precision medicine and immune therapies. Video Abstract: A combination of transcriptomics and mutational analyses in single cells from acute myeloid leukemia patients reveals the existence of distinct functional subsets and their associated drivers.
Date issued
2019-03
URI
https://hdl.handle.net/1721.1/125158
Department
Massachusetts Institute of Technology. Department of Chemistry; Massachusetts Institute of Technology. Institute for Medical Engineering & Science; Koch Institute for Integrative Cancer Research at MIT
Journal
Cell
Publisher
Elsevier BV
Citation
van Galen, Peter et al. "Single-Cell RNA-Seq Reveals AML Hierarchies Relevant to Disease Progression and Immunity." Cell 176, 6 (March 2019): P1265-1281.e24 © 2019 Elsevier Inc
Version: Author's final manuscript
ISSN
0092-8674

Collections
  • MIT Open Access Articles

Browse

All of DSpaceCommunities & CollectionsBy Issue DateAuthorsTitlesSubjectsThis CollectionBy Issue DateAuthorsTitlesSubjects

My Account

Login

Statistics

OA StatisticsStatistics by CountryStatistics by Department
MIT Libraries
PrivacyPermissionsAccessibilityContact us
MIT
Content created by the MIT Libraries, CC BY-NC unless otherwise noted. Notify us about copyright concerns.