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

Adult Base Sequence / genetics Bone Marrow Bone Marrow Cells / cytology Cell Line, Tumor Disease Progression Female Genotype Humans Leukemia, Myeloid, Acute / genetics Machine Learning Male Middle Aged Mutation Prognosis RNA Signal Transduction Single-Cell Analysis / methods Transcriptome / genetics Tumor Microenvironment Exome Sequencing / methods
acute myeloid leukemia cancer genetics genotyping immunity leukemia stem cells single-cell RNA-sequencing

Journal

Cell
ISSN: 1097-4172
Titre abrégé: Cell
Pays: United States
ID NLM: 0413066

Informations de publication

Date de publication:
07 03 2019
Historique:
received: 22 06 2018
revised: 07 12 2018
accepted: 17 01 2019
pmc-release: 07 03 2020
pubmed: 5 3 2019
medline: 7 1 2020
entrez: 5 3 2019
Statut: ppublish

Résumé

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.

Identifiants

DOI: 10.1016/j.cell.2019.01.031 PMID: 30827681 PMC: PMC6515904
pubmed: 30827681
pii: S0092-8674(19)30094-7
doi: 10.1016/j.cell.2019.01.031
pmc: PMC6515904
mid: NIHMS1524068
pii:
doi:

Substances chimiques

RNA 63231-63-0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1265-1281.e24

Subventions

Organisme : NCI NIH HHS
ID : DP1 CA216873
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA206963
Pays : United States
Organisme : NCI NIH HHS
ID : P01 CA066996
Pays : United States
Organisme : NHGRI NIH HHS
ID : R01 HG009269
Pays : United States
Organisme : NHGRI NIH HHS
ID : RM1 HG006193
Pays : United States
Organisme : NCI NIH HHS
ID : R37 CA225191
Pays : United States
Organisme : NCI NIH HHS
ID : U2C CA233195
Pays : United States

Informations de copyright

Copyright © 2019 Elsevier Inc. All rights reserved.

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Auteurs

Peter van Galen (P)

Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Ludwig Center at Harvard Medical School, Boston, MA 02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.

Volker Hovestadt (V)

Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Ludwig Center at Harvard Medical School, Boston, MA 02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.

Marc H Wadsworth Ii (MH)

Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Institute for Medical Engineering & Science, Department of Chemistry, and Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.

Travis K Hughes (TK)

Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Institute for Medical Engineering & Science, Department of Chemistry, and Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.

Gabriel K Griffin (GK)

Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Ludwig Center at Harvard Medical School, Boston, MA 02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Department of Pathology, Brigham and Women's Hospital, Boston, MA 02115, USA.

Sofia Battaglia (S)

Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Ludwig Center at Harvard Medical School, Boston, MA 02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.

Julia A Verga (JA)

Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Ludwig Center at Harvard Medical School, Boston, MA 02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.

Jason Stephansky (J)

Ludwig Center at Harvard Medical School, Boston, MA 02115, USA; Department of Pathology, Brigham and Women's Hospital, Boston, MA 02115, USA; Dana-Farber Cancer Institute, Boston, MA 02215, USA.

Timothy J Pastika (TJ)

Ludwig Center at Harvard Medical School, Boston, MA 02115, USA; Department of Pathology, Brigham and Women's Hospital, Boston, MA 02115, USA; Dana-Farber Cancer Institute, Boston, MA 02215, USA.

Jennifer Lombardi Story (J)

Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.

Geraldine S Pinkus (GS)

Department of Pathology, Brigham and Women's Hospital, Boston, MA 02115, USA.

Olga Pozdnyakova (O)

Department of Pathology, Brigham and Women's Hospital, Boston, MA 02115, USA.

Ilene Galinsky (I)

Dana-Farber Cancer Institute, Boston, MA 02215, USA.

Richard M Stone (RM)

Dana-Farber Cancer Institute, Boston, MA 02215, USA.

Timothy A Graubert (TA)

Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.

Alex K Shalek (AK)

Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Institute for Medical Engineering & Science, Department of Chemistry, and Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.

Jon C Aster (JC)

Ludwig Center at Harvard Medical School, Boston, MA 02115, USA; Department of Pathology, Brigham and Women's Hospital, Boston, MA 02115, USA.

Andrew A Lane (AA)

Ludwig Center at Harvard Medical School, Boston, MA 02115, USA; Dana-Farber Cancer Institute, Boston, MA 02215, USA.

Bradley E Bernstein (BE)

Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Ludwig Center at Harvard Medical School, Boston, MA 02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA. Electronic address: bernstein.bradley@mgh.harvard.edu.

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questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Single-Cell RNA-Seq Reveals AML Hierarchies...
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questionsmedicales.fr › Tumeurs › Tumeurs par type histologique › Leucémies › Leucémie myéloïde › Leucémie aigüe myéloïde › Single-Cell RNA-Seq Reveals AML Hierarchies...
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questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Adulte d'âge moyen › Single-Cell RNA-Seq Reveals AML Hierarchies...
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Mutation › Single-Cell RNA-Seq Reveals AML Hierarchies...
questionsmedicales.fr › Diagnostic › Pronostic › Single-Cell RNA-Seq Reveals AML Hierarchies...
questionsmedicales.fr › Acides nucléiques, nucléotides et nucléosides › Acides nucléiques › ARN › Single-Cell RNA-Seq Reveals AML Hierarchies...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Transduction du signal › Single-Cell RNA-Seq Reveals AML Hierarchies...
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questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Transcriptome › Single-Cell RNA-Seq Reveals AML Hierarchies...
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questionsmedicales.fr › Techniques d'investigation › Techniques génétiques › Analyse de séquence › Analyse de séquence d'ADN › Séquençage du génome entier › Séquençage de l'exome › Single-Cell RNA-Seq Reveals AML Hierarchies...