Development of a diagnostic test to detect a novel poor prognostic subgroup in pediatric AML

• Project/Area Number: 24591567
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: National Cancer Center Japan
• Principal Investigator: ICHIKAWA Hitoshi 独立行政法人国立がん研究センター, 研究所, 部門長 (30201924)
• Co-Investigator(Kenkyū-buntansha): HAYASHI Yasuhide 群馬県衛生環境研究所, 研究企画係, 研究員 (30238133)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 小児白血病 / 急性骨髄性白血病 / 遺伝子発現 / 予後因子 / 治療選択 / 層別化治療 / 融合遺伝子 / 小児AML

Outline of Final Research Achievements

From gene expression profiling data of 130 Japanese pediatric AML patients registered in AML99 study, we found that EVI1 and MEL1 were overexpressed in approximately 30% of patients, and that their high expression was significantly associated with inferior survival. Because of their mutually exclusive expression, a combined evaluation of their high expression enabled a clear distinction of patients with inferior survival (P<0.00001 in EFS and OS). This association was confirmed by quantitative RT-PCR analysis of 81 patients registered in AML-05 study (P=0.00017 in EFS, P=0.00028 in OS). We believe that the combined estimation of EVI1 and MEL1 expression will be an effective method for risk stratification of pediatric AML patients.

Research Products

• [Journal Article] High expression of EVI1 and MEL1 is a compelling poor prognostic marker of pediatric AML. (2015)
  • Author(s): Jo A, Mitani S, Shiba N, Hayashi Y, Hara Y, Takahashi H, Tsukimoto I, Tawa A, Horibe K, Tomizawa D, Taga T, Adachi S, Yoshida T, Ichikawa H
  • Journal Title: Leukemia Volume: 29 Issue: 5 Pages: 1067-1083
  • DOI: 10.1038/leu.2015.5
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] NUP98-NSD1 related gene expression signature is strongly associated with a poor prognosis in pediatric acute myeloid leukemia: a study of the Japanese Childhood AML Cooperative Study Group Cooperative Study Group (2013)
  • Author(s): Shiba N, Ichikawa H, Taki T, Park M, Jo A, Mitani S, Shimada A, Sotomatsu M, Arakawa H, Tabuchi K, Adachi S, Tawa A, Horibe K, Tsuchida M, Hanada R, Tsukimoto I, Hayashi Y
  • Journal Title: Genes Chromosomes Cancer Volume: 52 Issue: 7 Pages: 683-693
  • DOI: 10.1002/gcc.22064
  • Peer Reviewed
• [Presentation] Fusion gene finding in pediatric AML by RNA sequencing (2013)
  • Author(s): Sachiyo Mitani, Hiromi Sakamoto, Norio Shiba, Yasuhide Hayashi, Teruhiko Yoshida, Hitoshi Ichikawa
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: 横浜
• [Presentation] 2遺伝子の発現に基づく高リスク小児急性骨髄性白血病の同定 (2012)
  • Author(s): 三谷幸代、城 青衣、嶋田 明、柴 徳生、月本一郎、鶴澤正仁、林 泰秀、市川 仁
  • Organizer: 日本癌学会
  • Place of Presentation: 札幌