Number of RUNX1 mutations, wild-type allele loss and additional mutations impact on prognosis in adult RUNX1-mutated AML
Language English Country Great Britain, England Media print-electronic
Document type Journal Article
PubMed
28751771
DOI
10.1038/leu.2017.239
PII: leu2017239
Knihovny.cz E-resources
- MeSH
- Leukemia, Myeloid, Acute genetics pathology MeSH
- Alleles MeSH
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Mutation genetics MeSH
- Prognosis MeSH
- Core Binding Factor Alpha 2 Subunit genetics MeSH
- Repressor Proteins genetics MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Loss of Heterozygosity genetics MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Core Binding Factor Alpha 2 Subunit MeSH
- Repressor Proteins MeSH
- RUNX1 protein, human MeSH Browser
RUNX1-mutated acute myeloid leukemia (AML) show a distinct pattern of genetic abnormalities and an adverse prognosis. We analyzed the impact of multiple RUNX1 mutations and RUNX1 wild-type (WT) loss in 467 AML with RUNX1 mutations (mut): (1) RUNX1 WT loss (n=53), (2) >1 RUNX1mut (n=94) and (3) 1 RUNX1mut (n=323). In 1 RUNX1mut, +8 was most frequent, whereas in WT loss +13 was the most abundant trisomy (+8: 66% vs 31%, P=0.022; +13: 15% vs 62%, P<0.001). Analyses of 28 genes in 163 selected cases revealed SRSF2 (39%), ASXL1 (36%), DNMT3A (19%), IDH2 (17%) and SF3B1 (17%) as most frequently mutated genes. RUNX1 WT loss showed a higher frequency of ASXL1mut compared with the other cases (50% vs 29%, P=0.009). Median overall survival (OS) in the total cohort was 14 months. WT loss (OS: 5 months) and >1 RUNX1mut (14 months) showed an adverse impact on prognosis compared with 1 RUNX1mut (22 months; P=0.002 and 0.048, respectively). Mutations in ASXL1 and ⩾2 additional mutations correlated with shorter OS (10 vs 18 months, P=0.028; 12 vs 20 months, P=0.017). Thus, the number of RUNX1mut, RUNX1 WT loss and the number and type of additional mutations is biologically and clinically relevant.
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Nucleic Acids Res. 2010 Oct;38(18):6124-34 PubMed
N Engl J Med. 2015 Sep 17;373(12):1136-52 PubMed
Blood. 2014 Apr 3;123(14):2229-37 PubMed
Nat Genet. 1999 Oct;23(2):166-75 PubMed
Blood. 2004 Nov 15;104(10):3078-85 PubMed
J Clin Oncol. 2011 Apr 1;29(10):1364-72 PubMed
Blood. 2013 Nov 21;122(22):3616-27; quiz 3699 PubMed
Hematology Am Soc Hematol Educ Program. 2011;2011:36-42 PubMed
BMC Cancer. 2008 Oct 16;8:299 PubMed
Am J Hematol. 2012 Nov;87(11):1010-6 PubMed
Leukemia. 2010 Jan;24(1):242-6 PubMed
N Engl J Med. 2016 Jun 9;374(23 ):2209-2221 PubMed
Leukemia. 2016 Oct;30(10 ):2109-2112 PubMed
Structure. 1999 Oct 15;7(10):1247-56 PubMed
Int J Hematol. 2001 Oct;74(3):252-7 PubMed
Blood. 2009 Jan 29;113(5):1200-1 PubMed
Leukemia. 2010 Aug;24(8):1528-32 PubMed
J Clin Oncol. 2003 Jan 15;21(2):256-65 PubMed
Blood. 2016 May 19;127(20):2391-405 PubMed
Blood. 2010 Jul 22;116(3):354-65 PubMed
Blood. 2003 Jan 15;101(2):673-80 PubMed
Leukemia. 2002 Jan;16(1):53-9 PubMed
Nat Struct Biol. 2001 Apr;8(4):371-8 PubMed
Leukemia. 1995 Oct;9(10):1783-6 PubMed
Blood. 2016 Jan 7;127(1):29-41 PubMed
J Clin Oncol. 2012 Sep 20;30(27):3376-82 PubMed
Blood. 2000 Nov 1;96(9):3154-60 PubMed
Leukemia. 2016 Nov;30(11):2160-2168 PubMed
Leukemia. 2014 Feb;28(2):241-7 PubMed
N Engl J Med. 2013 May 30;368(22):2059-74 PubMed
Blood. 1999 Mar 15;93(6):1817-24 PubMed
Blood. 2007 Aug 15;110(4):1308-16 PubMed
Blood. 2008 Dec 1;112(12):4639-45 PubMed
Blood. 2011 Apr 14;117(15):e161-70 PubMed
Haematologica. 2011 Dec;96(12):1874-7 PubMed
Nucleic Acids Res. 2014 Jan;42(Database issue):D986-92 PubMed
