International Journal of Hematology

, Volume 98, Issue 4, pp 437–445 | Cite as

WT1 mutation in pediatric patients with acute myeloid leukemia: a report from the Japanese Childhood AML Cooperative Study Group

  • Hirozumi Sano
  • Akira Shimada
  • Ken Tabuchi
  • Tomohiko Taki
  • Chisato Murata
  • Myoung-ja Park
  • Kentaro Ohki
  • Manabu Sotomatsu
  • Souichi Adachi
  • Akio Tawa
  • Ryoji Kobayashi
  • Keizo Horibe
  • Masahiro Tsuchida
  • Ryoji Hanada
  • Ichiro Tsukimoto
  • Yasuhide HayashiEmail author
Original Article


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.


Acute myeloid leukemia WT1 mutation Cytogenetically normal acute myeloid leukemia Prognosis 



This work was supported by a grant for Cancer Research and a grant for Research on Children and Families from the Ministry of Health, Labor, and Welfare of Japan, a Grant-in-Aid for Scientific Research (B, C) and Exploratory Research from the Ministry of Education, Culture, Sports, Science, and Technology of Japan, and by a Research grant for Gunma Prefectural Hospitals.

Conflict of interest

There is no conflict of interest.


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Copyright information

© The Japanese Society of Hematology 2013

Authors and Affiliations

  • Hirozumi Sano
    • 1
    • 7
  • Akira Shimada
    • 1
    • 2
  • Ken Tabuchi
    • 3
  • Tomohiko Taki
    • 4
  • Chisato Murata
    • 1
  • Myoung-ja Park
    • 1
  • Kentaro Ohki
    • 1
  • Manabu Sotomatsu
    • 1
  • Souichi Adachi
    • 5
  • Akio Tawa
    • 6
  • Ryoji Kobayashi
    • 7
  • Keizo Horibe
    • 8
  • Masahiro Tsuchida
    • 9
  • Ryoji Hanada
    • 10
  • Ichiro Tsukimoto
    • 11
  • Yasuhide Hayashi
    • 1
    Email author
  1. 1.Department of Hematology/OncologyGunma Children’s Medical CenterShibukawaJapan
  2. 2.Department of Pediatrics/Pediatric Hematology & OncologyOkayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesOkayamaJapan
  3. 3.Department of HematologyKanagawa Children’s Medical CenterYokohamaJapan
  4. 4.Department of Molecular Diagnostics and TherapeuticsKyoto Prefectural University of Medicine, Graduate School of Medical ScienceKyotoJapan
  5. 5.Department of Human Health Sciences, Graduate School of MedicineKyoto UniversityKyotoJapan
  6. 6.Department of PediatricsNational Hospital Organization Osaka National HospitalOsakaJapan
  7. 7.Department of PediatricsSapporo Hokuyu HospitalSapporoJapan
  8. 8.Clinical Research CenterNational Hospital Organization Nagoya Medical CenterNagoyaJapan
  9. 9.Department of PediatricsIbaraki Children’s HospitalMitoJapan
  10. 10.Division of Hematology/OncologySaitama Children’s Medical CenterSaitamaJapan
  11. 11.First Department of PediatricsToho University School of MedicineTokyoJapan

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