International Journal of Hematology

, Volume 95, Issue 5, pp 509–515 | Cite as

RAS mutations are frequent in FAB type M4 and M5 of acute myeloid leukemia, and related to late relapse: a study of the Japanese Childhood AML Cooperative Study Group

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


Mutations in RAS are frequent in acute myeloid leukemia (AML), and are thought to contribute to leukemogenesis in a subset of patients; however, their prognostic significance has not been firmly established. One hundred and fifty-seven pediatric patients with AML were analyzed for NRAS and KRAS mutations around hot spots at codons 12, 13, and 61. Twenty-nine patients (18.5%) had an activating mutation of RAS. We found KRAS mutations to be more frequent than NRAS mutations (18/29, 62.1% of patients with RAS mutation), in contrast to previous reports (18–40%). The frequency of RAS mutation was higher in French-American-British types M4 and M5 than other types (P = 0.02). There were no significant differences in other clinical manifestations or distribution in cytogenetic subgroups, or aberrations of other genes, including KIT mutation, FLT3-ITD, and MLL-PTD, between patients with and without RAS mutations. No significant differences were observed in the 3-year overall survival and disease-free survival; however, the presence of RAS mutation was related to late relapse. The occurrence of clinical events at relatively late period should be monitored for in AML patients with mutations in RAS.


Acute myeloid leukemia RAS Late relapse Prognosis FAB 



Committee members of the Japanese Childhood AML Cooperative Study Group who contributed data to this study include Akira Morimoto, Department of Pediatrics, Kyoto Prefectural University of Medicine; Hiromasa Yabe, Department of Pediatrics, Tokai University School of Medicine; Kazuko Hamamoto, Department of Pediatrics, Hiroshima Red Cross Hospital; Shigeru Tsuchiya, Department of Pediatric Oncology, Institute of Development, Aging and Cancer, Tohoku University; Yuichi Akiyama, Department of Pediatrics, National Hospital Organization Kyoto Medical Center; Hisato Kigasawa, Department of Hematology, Kanagawa Children’s Medical Center; Akira Ohara, First Department of Pediatrics, Toho University School of Medicine; Hideki Nakayama, Department of Pediatrics, Hamanomachi Hospital; Kazuko Kudo, Department of Pediatrics, Nagoya University Graduate School of Medicine; and Masue Imaizumi, Department of Hematology/Oncology, Miyagi Prefectural Children’s Hospital. This work was supported by a grant for Cancer Research and a grant for Research on Children and Families from the Ministry of Health, Labour, 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 2012

Authors and Affiliations

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

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