Single-cell analysis based dissection of clonality in myelofibrosis.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
07 01 2020
07 01 2020
Historique:
received:
01
07
2019
accepted:
28
11
2019
entrez:
9
1
2020
pubmed:
9
1
2020
medline:
21
4
2020
Statut:
epublish
Résumé
Cancer development is an evolutionary genomic process with parallels to Darwinian selection. It requires acquisition of multiple somatic mutations that collectively cause a malignant phenotype and continuous clonal evolution is often linked to tumor progression. Here, we show the clonal evolution structure in 15 myelofibrosis (MF) patients while receiving treatment with JAK inhibitors (mean follow-up 3.9 years). Whole-exome sequencing at multiple time points reveal acquisition of somatic mutations and copy number aberrations over time. While JAK inhibition therapy does not seem to create a clear evolutionary bottleneck, we observe a more complex clonal architecture over time, and appearance of unrelated clones. Disease progression associates with increased genetic heterogeneity and gain of RAS/RTK pathway mutations. Clonal diversity results in clone-specific expansion within different myeloid cell lineages. Single-cell genotyping of circulating CD34 + progenitor cells allows the reconstruction of MF phylogeny demonstrating loss of heterozygosity and parallel evolution as recurrent events.
Identifiants
pubmed: 31911629
doi: 10.1038/s41467-019-13892-x
pii: 10.1038/s41467-019-13892-x
pmc: PMC6946829
doi:
Substances chimiques
Oncogene Protein p21(ras)
EC 3.6.5.2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
73Références
Cancer Discov. 2019 Aug;9(8):1050-1063
pubmed: 31088841
Science. 2008 Nov 28;322(5906):1377-80
pubmed: 19039135
Leukemia. 2019 May;33(5):1113-1123
pubmed: 30568172
J Clin Oncol. 1984 Jan;2(1):8-15
pubmed: 6699660
Nature. 2015 Feb 12;518(7538):240-4
pubmed: 25409150
Nature. 2011 Sep 11;478(7367):64-9
pubmed: 21909114
Genome Med. 2018 Apr 25;10(1):33
pubmed: 29695279
Genome Biol. 2017 Sep 19;18(1):178
pubmed: 28927434
N Engl J Med. 2013 Dec 19;369(25):2379-90
pubmed: 24325356
Mayo Clin Proc. 2017 Aug;92(8):1283-1290
pubmed: 28778261
Genomics. 2015 Mar;105(3):159-67
pubmed: 25576655
Science. 2001 Aug 3;293(5531):876-80
pubmed: 11423618
PLoS Genet. 2015 Dec 02;11(12):e1005657
pubmed: 26630308
Blood. 2011 Dec 15;118(25):6601-9
pubmed: 21963603
Nature. 2005 Apr 28;434(7037):1144-8
pubmed: 15793561
N Engl J Med. 2012 Mar 1;366(9):787-98
pubmed: 22375970
Nat Commun. 2017 Apr 21;8:15099
pubmed: 28429724
J Clin Invest. 2007 Sep;117(9):2562-9
pubmed: 17710227
Blood. 2007 Aug 15;110(4):1092-7
pubmed: 17488875
Nat Rev Cancer. 2006 Dec;6(12):924-35
pubmed: 17109012
Cell. 2011 Mar 4;144(5):646-74
pubmed: 21376230
Nat Rev Cancer. 2017 Oct;17(10):605-619
pubmed: 28912577
J Clin Oncol. 2019 Feb 10;37(5):375-385
pubmed: 30403573
Am J Hematol. 2018 Mar;93(3):348-355
pubmed: 29164670
Blood. 2017 Mar 23;129(12):1607-1616
pubmed: 28159736
PLoS Comput Biol. 2014 Aug 07;10(8):e1003665
pubmed: 25102416
Nat Rev Genet. 2017 Apr;18(4):213-229
pubmed: 28190876
Genome Res. 2015 Oct;25(10):1499-507
pubmed: 26430160
Blood. 2019 Mar 7;133(10):1140-1151
pubmed: 30610028
N Engl J Med. 2012 Mar 1;366(9):799-807
pubmed: 22375971
Nature. 2016 May 02;534(7605):47-54
pubmed: 27135926
Nat Med. 2019 Mar;25(3):517-525
pubmed: 30664780
Blood. 2007 Jul 1;110(1):375-9
pubmed: 17363731
Blood. 2017 Aug 31;130(9):1125-1131
pubmed: 28674026
Nat Genet. 2015 Dec;47(12):1402-7
pubmed: 26551669
N Engl J Med. 2015 Feb 12;372(7):601-612
pubmed: 25671252
Genome Res. 2013 Dec;23(12):2115-25
pubmed: 24056532
N Engl J Med. 2005 Feb 24;352(8):786-92
pubmed: 15728811
N Engl J Med. 2013 Dec 19;369(25):2391-2405
pubmed: 24325359
Science. 1976 Oct 1;194(4260):23-8
pubmed: 959840
N Engl J Med. 2018 Oct 11;379(15):1416-1430
pubmed: 30304655
Haematologica. 2019 May;104(5):e187-e190
pubmed: 30409794
Nature. 2019 Jan;565(7739):312-317
pubmed: 30602793
Ann Oncol. 2017 Dec 1;28(12):3076-3082
pubmed: 28950321
Nucleic Acids Res. 2013 Apr;41(7):e89
pubmed: 23471004
Blood. 2016 Dec 15;128(24):2863-2866
pubmed: 27784671
Annu Rev Med. 2015;66:129-43
pubmed: 25423595
Leukemia. 2018 Sep;32(9):1908-1919
pubmed: 29491455
Blood. 2014 Apr 3;123(14):2220-8
pubmed: 24478400
Nature. 2016 May 23;534(7607):402-6
pubmed: 27281199
Haematologica. 2015 Aug;100(8):1051-7
pubmed: 26001790
Blood. 2014 Feb 27;123(9):1372-83
pubmed: 24398328
Blood. 2013 Mar 21;121(12):2186-98
pubmed: 23319568
Blood. 2015 Sep 24;126(13):1551-4
pubmed: 26228487
Cancer Discov. 2014 Sep;4(9):1088-101
pubmed: 24920063
Nature. 2012 Jan 18;481(7381):306-13
pubmed: 22258609
F1000Res. 2016 Apr 19;5:
pubmed: 27134742
N Engl J Med. 2005 Apr 28;352(17):1779-90
pubmed: 15858187