title: WT1 mutation in pediatric patients with acute myeloid leukemia: a report from the Japanese Childhood AML Cooperative Study Group.
abstract: Mutations in Wilms tumor 1 (WT1) have been reported in 10-22 % of patients with cytogenetically normal acute myeloid leukemia (CN-AML), but the prognostic implications of these abnormalities have not been clarified in either adults or children. One hundred and fifty-seven pediatric AML patients were analyzed for WT1 mutations around hotspots at exons 7 and 9; however, amplification of the WT1 gene by the reverse transcriptase-polymerase chain reaction was not completed in four cases (2.5 %). Of the 153 evaluable patients, 10 patients (6.5 %) had a mutation in WT1. The incidence of WT1 mutations was significantly higher in CN-AML than in others (15.2 vs. 4.5 %, respectively, P = 0.03). Of the 10 WT1-mutated cases, eight (80 %) had mutations in other genes, including FLT3-ITD in two cases, FLT3-D835 mutation in two, KIT mutation in three, MLL-PTD in three, NRAS mutation in one, and KRAS mutation in two (in some cases, more than one additional gene was mutated). The incidences of KIT and FLT3-D835 mutations were significantly higher in patients with than in those without WT1 mutation. No significant differences were observed in the 3-year overall survival and disease-free survival; however, the presence of WT1 mutation was related to a poor prognosis in patients with CN-AML, excluding those with FLT3-ITD and those younger than 3 years.
authors: Department of Hematology/Oncology, Gunma Children's Medical Center, 779 Shimohakoda, Hokkitsu, Shibukawa, Gunma, 377-8577, Japan.
authors: Hirozumi
authors: H
authors: Sano
authors: Akira
authors: A
authors: Shimada
authors: Ken
authors: K
authors: Tabuchi
authors: Tomohiko
authors: T
authors: Taki
authors: Chisato
authors: C
authors: Murata
authors: Myoung-ja
authors: MJ
authors: Park
authors: Kentaro
authors: K
authors: Ohki
authors: Manabu
authors: M
authors: Sotomatsu
authors: Souichi
authors: S
authors: Adachi
authors: Akio
authors: A
authors: Tawa
authors: Ryoji
authors: R
authors: Kobayashi
authors: Keizo
authors: K
authors: Horibe
authors: Masahiro
authors: M
authors: Tsuchida
authors: Ryoji
authors: R
authors: Hanada
authors: Ichiro
authors: I
authors: Tsukimoto
authors: Yasuhide
authors: Y
authors: Hayashi
mesh_terms: D000293:Adolescent; D044466:Asian People / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D002871:Chromosome Banding; D005260:Female; D015870:Gene Expression; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007564:Japan; D007621:Karyotyping; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000401:mortality; D008297:Male; D009154:Mutation; D063868:Patient Outcome Assessment; D011379:Prognosis; D016016:Proportional Hazards Models; D025721:WT1 Proteins / Q000235:genetics*
chemical_list: D025721:WT1 Proteins
references: Pediatr Blood Cancer. 2007 Apr;48(4):393-8
references: 16550530
references: Leukemia. 2005 Dec;19(12):2090-100
references: 16304571
references: Blood. 2006 Apr 15;107(8):3303-12
references: 16380455
references: J Clin Oncol. 2008 Nov 20;26(33):5429-35
references: 18591546
references: Blood. 2010 Aug 5;116(5):702-10
references: 20413658
references: Br J Haematol. 1999 Apr;105(1):155-62
references: 10233379
references: Leukemia. 2009 Aug;23(8):1472-9
references: 19322206
references: Br J Haematol. 2004 Jun;125(5):590-600
references: 15147374
references: Leukemia. 2008 May;22(5):915-31
references: 18288131
references: Blood. 2004 Feb 1;103(3):1085-8
references: 14504097
references: J Clin Oncol. 2009 Aug 20;27(24):4007-13
references: 19620491
references: Blood. 2008 Feb 1;111(3):1044-53
references: 18000167
references: Expert Rev Mol Med. 2007 May 24;9(14):1-17
references: 17524167
references: J Clin Oncol. 2007 Aug 1;25(22):3337-43
references: 17577018
references: Leukemia. 2005 Dec;19(12):2130-8
references: 16304572
references: Pediatr Blood Cancer. 2009 Dec;53(6):1136-9
references: 19618455
references: Cell. 1990 Jun 29;61(7):1257-69
references: 2163761
references: Cell. 1990 Feb 9;60(3):509-20
references: 2154335
references: Pediatr Blood Cancer. 2008 Feb;50(2):264-9
references: 17763464
references: Blood. 2009 May 7;113(19):4505-11
references: 19221039
references: Int J Hematol. 2012 Oct;96(4):469-76
references: 22915059
references: Leukemia. 2007 May;21(5):868-76
references: 17361230
references: Science. 1994 Apr 15;264(5157):436-40
references: 8153634
references: Blood. 1998 Oct 1;92(7):2322-33
references: 9746770
references: Blood. 2011 Nov 24;118(22):5905-13
references: 21967978
references: Int J Hematol. 2012 May;95(5):509-15
references: 22407852
references: Blood. 2006 Mar 1;107(5):1806-9
references: 16291592
references: Blood. 1996 Apr 1;87(7):2878-84
references: 8639907
references: Blood. 2007 Jan 15;109(2):431-48
references: 16960150
references: Lancet Oncol. 2010 Jun;11(6):543-52
references: 20451454
references: J Clin Oncol. 2008 Oct 1;26(28):4595-602
references: 18559874
references: Leukemia. 2007 Mar;21(3):550-1; author reply 552
references: 17205055
references: Nature. 1994 Apr 21;368(6473):753-6
references: 8152487
references: Proc Natl Acad Sci U S A. 1994 Nov 8;91(23):11045-9
references: 7972006
references: J Clin Oncol. 2006 Sep 20;24(27):4499-506
references: 16983120
references: Blood. 2009 Jun 4;113(23):5951-60
references: 19171881