Clonal evolution of acute myeloid leukemia revealed by high-throughput single-cell genomics.
Aged
Animals
Clonal Evolution
/ drug effects
Cohort Studies
Female
Genetic Association Studies
Genomics
Heterografts
High-Throughput Nucleotide Sequencing
Humans
Leukemia, Myeloid, Acute
/ drug therapy
Male
Mice
Mice, Inbred NOD
Middle Aged
Models, Genetic
Mutation
Sequence Analysis, DNA
Single-Cell Analysis
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
21 10 2020
21 10 2020
Historique:
received:
04
08
2020
accepted:
22
09
2020
entrez:
22
10
2020
pubmed:
23
10
2020
medline:
11
11
2020
Statut:
epublish
Résumé
Clonal diversity is a consequence of cancer cell evolution driven by Darwinian selection. Precise characterization of clonal architecture is essential to understand the evolutionary history of tumor development and its association with treatment resistance. Here, using a single-cell DNA sequencing, we report the clonal architecture and mutational histories of 123 acute myeloid leukemia (AML) patients. The single-cell data reveals cell-level mutation co-occurrence and enables reconstruction of mutational histories characterized by linear and branching patterns of clonal evolution, with the latter including convergent evolution. Through xenotransplantion, we show leukemia initiating capabilities of individual subclones evolving in parallel. Also, by simultaneous single-cell DNA and cell surface protein analysis, we illustrate both genetic and phenotypic evolution in AML. Lastly, single-cell analysis of longitudinal samples reveals underlying evolutionary process of therapeutic resistance. Together, these data unravel clonal diversity and evolution patterns of AML, and highlight their clinical relevance in the era of precision medicine.
Identifiants
pubmed: 33087716
doi: 10.1038/s41467-020-19119-8
pii: 10.1038/s41467-020-19119-8
pmc: PMC7577981
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
5327Subventions
Organisme : NCI NIH HHS
ID : P30 CA016672
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA100632
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA193235
Pays : United States
Organisme : NIH HHS
ID : S10 OD024977
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA255721
Pays : United States
Commentaires et corrections
Type : ErratumIn
Type : ErratumIn
Références
Nature. 2019 Jul;571(7765):355-360
pubmed: 31270458
Cell. 2017 Feb 9;168(4):613-628
pubmed: 28187284
Cell. 2012 Jul 20;150(2):264-78
pubmed: 22817890
N Engl J Med. 2017 Feb 9;376(6):536-547
pubmed: 28177873
N Engl J Med. 2012 Mar 8;366(10):883-892
pubmed: 22397650
Blood. 2010 Aug 5;116(5):702-10
pubmed: 20413658
Bone Marrow Transplant. 2013 Mar;48(3):452-8
pubmed: 23208313
Nature. 2015 Feb 19;518(7539):422-6
pubmed: 25470049
Mol Cell. 2015 May 21;58(4):598-609
pubmed: 26000845
Nat Methods. 2016 Jun;13(6):505-7
pubmed: 27088313
Cell. 2012 May 25;149(5):994-1007
pubmed: 22608083
Leukemia. 2011 Feb;25(2):246-53
pubmed: 21079611
Nature. 2010 Oct 28;467(7319):1109-13
pubmed: 20981101
Cancer Discov. 2019 Aug;9(8):1050-1063
pubmed: 31088841
Cancer Cell. 2014 Mar 17;25(3):379-92
pubmed: 24613412
Proc Natl Acad Sci U S A. 2010 Sep 28;107(39):16910-5
pubmed: 20837533
Nature. 2011 Jan 20;469(7330):356-61
pubmed: 21160474
Leukemia. 2019 May;33(5):1113-1123
pubmed: 30568172
Nat Rev Cancer. 2015 Mar;15(3):152-65
pubmed: 25693834
Genome Res. 2018 Sep;28(9):1345-1352
pubmed: 30087104
Cell. 2019 Mar 7;176(6):1265-1281.e24
pubmed: 30827681
Genome Biol. 2016 May 05;17:86
pubmed: 27149953
Nature. 2014 Feb 20;506(7488):328-33
pubmed: 24522528
Cell Stem Cell. 2018 Nov 1;23(5):700-713.e6
pubmed: 30388424
Nature. 2011 Apr 7;472(7341):90-4
pubmed: 21399628
Nat Med. 2015 Jul;21(7):751-9
pubmed: 26099045
Nature. 2014 Aug 14;512(7513):155-60
pubmed: 25079324
Leukemia. 2015 Dec;29(12):2390-2
pubmed: 26108694
Blood Adv. 2019 Feb 12;3(3):339-349
pubmed: 30709865
Exp Hematol. 2014 Jun;42(6):457-63
pubmed: 24495871
Nat Med. 2018 Aug;24(8):1167-1177
pubmed: 30013198
Blood. 2017 Aug 10;130(6):732-741
pubmed: 28588019
Lancet Oncol. 2017 Jan;18(1):100-111
pubmed: 27923552
Sci Transl Med. 2015 Apr 1;7(281):281re2
pubmed: 25834112
N Engl J Med. 2005 Jan 20;352(3):254-66
pubmed: 15659725
Nat Commun. 2019 Jun 21;10(1):2750
pubmed: 31227714
Biol Blood Marrow Transplant. 2018 Jul;24(7):1514-1520
pubmed: 29448058
Nature. 2019 May;569(7757):576-580
pubmed: 31092926
Nucleic Acids Res. 2013 Sep;41(17):e165
pubmed: 23892400