Mutation signatures of pediatric acute myeloid leukemia and normal blood progenitors associated with differential patient outcomes.
AML
HSC
childhood leukemia
human hematopoiesis
mutational processes
somatic mutations
Journal
Blood cancer discovery
ISSN: 2643-3249
Titre abrégé: Blood Cancer Discov
Pays: United States
ID NLM: 101764786
Informations de publication
Date de publication:
09 2021
09 2021
Historique:
entrez:
13
10
2021
pubmed:
14
10
2021
medline:
14
10
2021
Statut:
ppublish
Résumé
Acquisition of oncogenic mutations with age is believed to be rate limiting for carcinogenesis. However, the incidence of leukemia in children is higher than in young adults. Here we compare somatic mutations across pediatric acute myeloid leukemia (pAML) patient-matched leukemic blasts and hematopoietic stem and progenitor cells (HSPCs), as well as HSPCs from age-matched healthy donors. HSPCs in the leukemic bone marrow have limited genetic relatedness and share few somatic mutations with the cell-of-origin of the malignant blasts, suggesting polyclonal hematopoiesis in pAML patients. Compared to normal HSPCs, a subset of pAML cases harbored more somatic mutations and a distinct composition of mutational process signatures. We hypothesize these cases might have arisen from a more committed progenitor. This subset had better outcomes than pAML cases with mutation burden comparable to age-matched healthy HSPCs. Our study provides insights into the etiology and patient stratification of pAML.
Identifiants
pubmed: 34642666
doi: 10.1158/2643-3230.BCD-21-0010
pmc: PMC7611805
mid: EMS135524
pii: 2643-3230.BCD-21-0010
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Pagination
484-499Subventions
Organisme : European Research Council
ID : 864499
Pays : International
Organisme : Dutch Research Council
ID : NWO_016.VIDI.171.023
Pays : Netherlands
Déclaration de conflit d'intérêts
Declaration of interests Authors declare no competing interests.
Références
Expert Rev Anticancer Ther. 2018 Mar;18(3):277-293
pubmed: 29338495
Science. 2015 Jan 2;347(6217):78-81
pubmed: 25554788
J Clin Med. 2015 Jan 09;4(1):127-49
pubmed: 26237023
Nat Commun. 2019 Jul 5;10(1):2969
pubmed: 31278357
Genome Biol. 2014;15(12):550
pubmed: 25516281
Cell Rep. 2018 Nov 27;25(9):2308-2316.e4
pubmed: 30485801
Biochem Biophys Res Commun. 1986 Feb 26;135(1):330-5
pubmed: 3954778
Nat Rev Clin Oncol. 2019 Apr;16(4):227-240
pubmed: 30546053
Sci Rep. 2020 Jul 31;10(1):12991
pubmed: 32737409
Genome Res. 2013 May;23(5):843-54
pubmed: 23382536
J Cell Sci. 2006 Jan 1;119(Pt 1):124-31
pubmed: 16371652
Nat Protoc. 2018 Jan;13(1):59-78
pubmed: 29215633
Nature. 2016 Oct 13;538(7624):260-264
pubmed: 27698416
J Clin Invest. 2006 Oct;116(10):2808-16
pubmed: 17016561
Nat Rev Cancer. 2018 Aug;18(8):471-484
pubmed: 29784935
Leuk Lymphoma. 2018 Jul;59(7):1690-1699
pubmed: 29058513
Bioinformatics. 2010 Mar 1;26(5):589-95
pubmed: 20080505
Cell. 2012 Jul 20;150(2):264-78
pubmed: 22817890
Biochim Biophys Acta Rev Cancer. 2017 Apr;1867(2):84-94
pubmed: 28167050
Stem Cells Transl Med. 2017 Aug;6(8):1661-1665
pubmed: 28682009
Proc Natl Acad Sci U S A. 2000 Jun 20;97(13):7521-6
pubmed: 10861016
Nat Genet. 2015 Dec;47(12):1402-7
pubmed: 26551669
J Pathol. 2017 May;242(1):10-15
pubmed: 28127763
Exp Hematol. 2018 Dec;68:51-61
pubmed: 30243574
Nature. 2018 Mar 15;555(7696):371-376
pubmed: 29489755
Biostatistics. 2017 Apr 1;18(2):275-294
pubmed: 27756721
Nat Genet. 2011 May;43(5):491-8
pubmed: 21478889
Bioinformatics. 2016 Sep 15;32(18):2847-9
pubmed: 27207943
Nature. 2020 Feb;578(7793):94-101
pubmed: 32025018
Leukemia. 2013 Apr;27(4):852-60
pubmed: 23235717
Best Pract Res Clin Haematol. 2019 Jun;32(2):177-185
pubmed: 31203999
Nature. 2017 Mar 30;543(7647):714-718
pubmed: 28329761
Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15545-50
pubmed: 16199517
Nature. 2014 Feb 20;506(7488):328-33
pubmed: 24522528
Cell. 2019 May 2;177(4):821-836.e16
pubmed: 30982602
Genome Med. 2018 Apr 25;10(1):33
pubmed: 29695279
Leukemia. 2016 Jan;30(1):250-3
pubmed: 26050648
Cancer Res. 2016 Apr 15;76(8):2197-205
pubmed: 26941285
Cells. 2019 Jan 03;8(1):
pubmed: 30609792
Nat Med. 2018 Jan;24(1):103-112
pubmed: 29227476
Proc Natl Acad Sci U S A. 2016 Jan 26;113(4):1050-5
pubmed: 26755588
Nature. 2018 Mar 15;555(7696):321-327
pubmed: 29489754
Nature. 2018 Sep;561(7724):473-478
pubmed: 30185910
Nat Rev Cancer. 2013 May;13(5):357-65
pubmed: 23612461
Nature. 2013 Aug 22;500(7463):415-21
pubmed: 23945592
Bioinformatics. 2017 Sep 15;33(18):2938-2940
pubmed: 28645171
Leukemia. 2013 Apr;27(5):1000-8
pubmed: 23212154
Mol Syst Biol. 2018 Mar 15;14(3):e8041
pubmed: 29545397
Biochem Pharmacol. 2001 Apr 15;61(8):1033-40
pubmed: 11286995
Blood. 2012 Dec 13;120(25):4973-81
pubmed: 23091297
Nat Rev Genet. 2014 Sep;15(9):585-98
pubmed: 24981601
Leukemia. 2006 Jul;20(7):1310-3
pubmed: 16628191
J Clin Oncol. 2015 Sep 20;33(27):2949-62
pubmed: 26304895
Cell. 2012 May 25;149(5):994-1007
pubmed: 22608083