PAX5-driven subtypes of B-progenitor acute lymphoblastic leukemia.
Acute Disease
Adolescent
Adult
Aged
Animals
Child
Child, Preschool
Chromosomes
/ genetics
Female
Gene Rearrangement
/ genetics
Humans
Infant
Male
Mice
Mice, Inbred C57BL
Middle Aged
Mutation
/ genetics
PAX5 Transcription Factor
/ genetics
Precursor B-Cell Lymphoblastic Leukemia-Lymphoma
/ genetics
Transcriptome
/ genetics
Young Adult
Journal
Nature genetics
ISSN: 1546-1718
Titre abrégé: Nat Genet
Pays: United States
ID NLM: 9216904
Informations de publication
Date de publication:
02 2019
02 2019
Historique:
received:
01
08
2018
accepted:
13
11
2018
pubmed:
16
1
2019
medline:
25
4
2019
entrez:
16
1
2019
Statut:
ppublish
Résumé
Recent genomic studies have identified chromosomal rearrangements defining new subtypes of B-progenitor acute lymphoblastic leukemia (B-ALL), however many cases lack a known initiating genetic alteration. Using integrated genomic analysis of 1,988 childhood and adult cases, we describe a revised taxonomy of B-ALL incorporating 23 subtypes defined by chromosomal rearrangements, sequence mutations or heterogeneous genomic alterations, many of which show marked variation in prevalence according to age. Two subtypes have frequent alterations of the B lymphoid transcription-factor gene PAX5. One, PAX5alt (7.4%), has diverse PAX5 alterations (rearrangements, intragenic amplifications or mutations); a second subtype is defined by PAX5 p.Pro80Arg and biallelic PAX5 alterations. We show that p.Pro80Arg impairs B lymphoid development and promotes the development of B-ALL with biallelic Pax5 alteration in vivo. These results demonstrate the utility of transcriptome sequencing to classify B-ALL and reinforce the central role of PAX5 as a checkpoint in B lymphoid maturation and leukemogenesis.
Identifiants
pubmed: 30643249
doi: 10.1038/s41588-018-0315-5
pii: 10.1038/s41588-018-0315-5
pmc: PMC6525306
mid: NIHMS1016441
doi:
Substances chimiques
PAX5 Transcription Factor
0
PAX5 protein, human
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
296-307Subventions
Organisme : NCI NIH HHS
ID : P30 CA016672
Pays : United States
Organisme : NCI NIH HHS
ID : R35 CA197695
Pays : United States
Organisme : NCI NIH HHS
ID : UG1 CA189859
Pays : United States
Organisme : NCI NIH HHS
ID : U24 CA196172
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA021765
Pays : United States
Organisme : NCI NIH HHS
ID : U10 CA180790
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA016058
Pays : United States
Organisme : NCI NIH HHS
ID : U10 CA180899
Pays : United States
Organisme : NCI NIH HHS
ID : UG1 CA233332
Pays : United States
Organisme : NCI NIH HHS
ID : U10 CA180886
Pays : United States
Organisme : NIGMS NIH HHS
ID : P50 GM115279
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Organisme : NCI NIH HHS
ID : U10 CA180791
Pays : United States
Organisme : NCI NIH HHS
ID : RC1 CA145707
Pays : United States
Organisme : NCI NIH HHS
ID : U10 CA180820
Pays : United States
Références
Annu Rev Immunol. 2001;19:595-621
pubmed: 11244048
Proc Natl Acad Sci U S A. 2002 May 14;99(10):6567-72
pubmed: 12011421
Blood. 2004 Jun 15;103(12):4396-407
pubmed: 14551133
Genes Dev. 1992 Sep;6(9):1589-607
pubmed: 1516825
Cancer. 2004 Dec 15;101(12):2788-801
pubmed: 15481055
Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15545-50
pubmed: 16199517
J Biol Chem. 2006 Aug 18;281(33):23922-31
pubmed: 16707490
Nature. 2007 Apr 12;446(7137):758-64
pubmed: 17344859
Leukemia. 2007 Jun;21(6):1258-66
pubmed: 17443227
Immunity. 2007 Jul;27(1):49-63
pubmed: 17658281
Genome Res. 2007 Nov;17(11):1665-74
pubmed: 17921354
Blood. 2008 Feb 15;111(4):1827-33
pubmed: 18048644
Bioinformatics. 2009 Feb 1;25(3):315-21
pubmed: 19052058
N Engl J Med. 2009 Jan 29;360(5):470-80
pubmed: 19129520
Lancet Oncol. 2009 Feb;10(2):125-34
pubmed: 19138562
Bioinformatics. 2009 Jul 15;25(14):1754-60
pubmed: 19451168
Bioinformatics. 2009 Aug 15;25(16):2078-9
pubmed: 19505943
N Engl J Med. 2009 Jun 25;360(26):2730-41
pubmed: 19553647
Blood. 2009 Sep 10;114(11):2273-9
pubmed: 19597184
Blood. 2010 Sep 23;116(12):2070-7
pubmed: 20466853
Genome Res. 2010 Sep;20(9):1297-303
pubmed: 20644199
J Clin Oncol. 2010 Aug 20;28(24):3880-9
pubmed: 20660823
Genome Biol. 2010;11(10):R106
pubmed: 20979621
Nat Biotechnol. 2011 Jan;29(1):24-6
pubmed: 21221095
Cell. 2011 Jan 21;144(2):296-309
pubmed: 21241896
Genome Biol. 2011;12(1):R6
pubmed: 21247443
Pediatr Blood Cancer. 2011 Oct;57(4):569-77
pubmed: 21360654
Nat Genet. 2011 May;43(5):491-8
pubmed: 21478889
Bioinformatics. 2012 Mar 15;28(6):882-3
pubmed: 22257669
Bioinformatics. 2012 Aug 15;28(16):2209-10
pubmed: 22743224
Cancer Cell. 2012 Aug 14;22(2):153-66
pubmed: 22897847
Bioinformatics. 2013 Jan 1;29(1):15-21
pubmed: 23104886
Nat Genet. 2013 Mar;45(3):242-52
pubmed: 23334668
Bioinformatics. 2013 Oct 1;29(19):2482-4
pubmed: 23926227
J Cell Sci. 2013 Nov 1;126(Pt 21):5074-85
pubmed: 24006257
Nat Genet. 2013 Oct;45(10):1226-1231
pubmed: 24013638
Leukemia. 2014 May;28(5):1015-21
pubmed: 24166298
Mol Cancer Res. 2014 Apr;12(4):595-606
pubmed: 24435167
Bioinformatics. 2014 May 15;30(10):1473-5
pubmed: 24463181
Nat Genet. 2014 Mar;46(3):287-93
pubmed: 24509477
Nat Commun. 2014 Mar 24;5:3469
pubmed: 24662245
N Engl J Med. 2014 Sep 11;371(11):1005-15
pubmed: 25207766
Bioinformatics. 2015 Jan 15;31(2):166-9
pubmed: 25260700
Immunity. 2015 Jan 20;42(1):18-27
pubmed: 25607456
Blood. 2015 Jun 4;125(23):3609-17
pubmed: 25855603
Leukemia. 2015 Dec;29(12):2445-8
pubmed: 25943178
Cancer Cell. 2015 Sep 14;28(3):343-56
pubmed: 26321221
N Engl J Med. 2015 Oct 15;373(16):1541-52
pubmed: 26465987
Cancer Cell. 2016 Feb 8;29(2):186-200
pubmed: 26859458
Nat Genet. 2016 May;48(5):569-74
pubmed: 27019113
J Clin Oncol. 2016 Jul 10;34(20):2380-8
pubmed: 27114587
Nat Commun. 2016 Jun 06;7:11790
pubmed: 27265895
J Clin Oncol. 2016 Oct 1;34(28):3451-9
pubmed: 27507882
Nat Genet. 2016 Dec;48(12):1481-1489
pubmed: 27776115
Nat Commun. 2016 Nov 08;7:13331
pubmed: 27824051
J Clin Oncol. 2017 Mar 20;35(9):975-983
pubmed: 28297628
Curr Opin Hematol. 2017 Jul;24(4):345-352
pubmed: 28463873
Blood. 2017 Sep 21;130(12):1395-1401
pubmed: 28778863
Nature. 2018 Oct;562(7727):373-379
pubmed: 30209392
Bioinformatics. 2019 Jan 1;35(1):126-129
pubmed: 30561549
Cancer Chemother Rep. 1966 Mar;50(3):163-70
pubmed: 5910392
Cell. 1994 Dec 2;79(5):901-12
pubmed: 8001127
Genes Dev. 1997 Feb 15;11(4):476-91
pubmed: 9042861