Establishment of new system for genomic analysis for AML using by desk-top next generation sequencer

• Project/Area Number: 26670277
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Laboratory medicine
• Research Institution: Kyoto University
• Principal Investigator: ADACHI Souichi 京都大学, 医学(系)研究科(研究院), 教授 (10273450)
• Co-Investigator(Kenkyū-buntansha): SHIMADA Akirara 岡山大学, 医学研究科, 講師 (70391836)
• Project Period (FY): 2014-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2014: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
• Keywords: 次世代シークエンサー / 予後因子 / AML / 遺伝子検査学

Outline of Final Research Achievements

It is necessary for clinical studies to analyze many genomic genes analysis at the same time by using next-generation sequencer. For the purpose of establishing new methods to analyze many genes quickly and less expensively, we made gene analysis panels for child acute myeloid leukemia patients by desk-top next generation sequencer. We selected 150 genes from DNA samples of AML (primary, remission and relapse) by using Haloplex customized panel of Agilent Co. We analyzed 8 cases of AML and detected IKZF, KRAS, GATA1, KIT, PU.1 mutation in four cases. We also detected large deletions of SH2B3 and SMARCB3 genes in the other four cases. We are going to analyze many samples from JPLSG AML-05 studies by the panel using desk-top next generation sequencer.

Research Products

• [Journal Article] Adverse Prognostic Impact of KIT Mutations in Childhood CBF-AML: the Results of the Japanese Pediatric Leukemia/Lymphoma Study Group AML-05 Trial. (2015)
  • Author(s): Tokumasu M, Murata C, Shimada A, Ohki K, Hayashi Y, Saito AM, Fujimoto J, Horibe K, Nagao M, Itoh H, Kamikubo Y, Nakayama H, Kinoshita A, Tomizawa D, Taga1 T, Tawa A, Tanaka S, Heike T,and Adachi S
  • Journal Title: Leukemia Volume: 未定
  • Peer Reviewed
• [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] EVI1 overexpression is a poor prognostic factor in pediatric patients with mixed lineage leukemia-AF9 rearranged acute myeloid leukemia. (2014)
  • Author(s): Matsuo H, Kajihara M, Tomizawa D, Watanabe T, Saito AM, Fujimoto J, Horibe K, Kodama K, Tokumasu M, Itoh H, Nakayama H, Kinoshita A, Taga T, Tawa A, Taki T, Shiba N, Ohki K, Hayashi Y, Yamashita Y, Shimada A, Tanaka S, Adachi S.
  • Journal Title: Haematologica Volume: 99 Issue: 11 Pages: 225-227
  • DOI: 10.3324/haematol.2014.107128
  • Peer Reviewed / Open Access
• [Journal Article] Outcome of children with relapsed acute myeloid leukemia following initial therapy under the AML99 protocol (2014)
  • Author(s): Nakayama H, Tabuchi K, Tawa A, Tsukimoto I, Tsuchida M, Morimoto A, Yabe H, Horibe K, Hanada R, Imaizumi M, Hayashi Y, Hamamoto K, Kobayashi R, Kudo K, Shimada A, Miyamura T, Moritake H, Tomizawa D, Taga T, Adachi S.
  • Journal Title: Int J Hematol Volume: 100(2) Issue: 2 Pages: 171-9
  • DOI: 10.1007/s12185-014-1616-9
  • Peer Reviewed / Open Access
• [Journal Article] Prognostic implications of CEBPA mutations in pediatric acute myeloid leukemia: a report from the Japanese Pediatric Leukemia/Lymphoma Study Group. (2014)
  • Author(s): Matsuo H, Kajihara M, Tomizawa D, Watanabe T, Saito AM, Fujimoto J, Horibe K, Kodama K, Tokumasu M, Itoh H, Nakayama H, Kinoshita A, Taga T, Tawa A, Taki T, Tanaka S, Adachi S.
  • Journal Title: Blood Cancer J Volume: 4 Issue: 7 Pages: e226-e226
  • DOI: 10.1038/bcj.2014.47
  • Peer Reviewed / Open Access
• [Presentation] Poor prognosis associated with FAB subtypes M4 and M5 in Japanese pediatric acute myeloid leukemia patients with FLT3-ITD. (2014)
  • Author(s): Hara Y, Shiba N, Ohki K, Park M-J, Shimada A, Tomizawa D, Saito AM, Fujimoto J, Taki T, Kinoshita A, Taga T, Arakawa H, Tawa A, Horibe K, Adachi S, Hayashi Y.
  • Organizer: 56th Annual Meeting of the American Society of Hematology
  • Place of Presentation: San Francisco
  • Year and Date: 2014-12-06 – 2014-12-09
• [Presentation] Clinical features of patients with ASXL1 and ASXL2 mutations in pediatric acute myeloid leukemia. (2014)
  • Author(s): Yamato G, Shiba N, Yoshida K, Ohki K, Park M-J, Hara Y, Tomizawa D, Sotomatsu M, Taga T, Adachi S, Tawa A, Horibe K, Arakawa H, Ogawa S, Hayashi Y.
  • Organizer: 56th Annual Meeting of the American Society of Hematology
  • Place of Presentation: San Francisco
  • Year and Date: 2014-12-06 – 2014-12-09
• [Presentation] Pediatric acute megakaryoblastic leukemia without Down syndrome: a retrospective study by the International Berlin-Frankfurt-Munster Study Group (I-BFMSG). (2014)
  • Author(s): Inaba H, Zhou Y, Abla O, Adachi S, Auvrignon A, Beverloo HB, de Bont E, Chang T-T, Creutzig U, Dastugue N, Dworzak M, Elitzur S, Fynn A, Forestier E, Hasle H, Liang D-C, Lee V, Locatelli F, Masetti R, De Moerloose B, Reinhardt D, Rodriguez L, Shen S, Taga T, Tomizawa D, Yeoh AEJ, Zimmermann M, Raimondi SC.
  • Organizer: 56th Annual Meeting of the American Society of Hematology
  • Place of Presentation: San Francisco
  • Year and Date: 2014-12-06 – 2014-12-09
• [Presentation] Pediatric AML with FLT3-ITD/WT, NUP98-NSD1, NPM1, and WT1 mutations affected the clinical outcome. (2014)
  • Author(s): Shimada A, Yamashita Y, Tomizawa D, Shiba N, Tawa A, Watanabe T, Yokozawa T, Kudo K, Taga T, Iwamoto S, Terui K, Moritake H, Kinoshita A, Takahashi H, Nakayama H, Koh K, Goto H, Kosaka Y, Saito AM, Fujimoto J, Horibe K, Hara Y, Oki K, Hayashi Y, Adachi S.
  • Organizer: 第76回日本血液学会総会
  • Place of Presentation: 大阪
  • Year and Date: 2014-10-31 – 2014-11-02
• [Presentation] The prognostic impact of high EVI1-related genes expression in pediatric acute myeloid leukemia. (2014)
  • Author(s): Shiba N, Hara Y, Ohki K, Yamato G, Park M-J, Kobayashi T, Ichikawa H, Tomizawa D, Taki T, Shimada A, Sotomatsu M, Arakawa H, Horibe K, Adachi S, Tawa A, Hayashi Y.
  • Organizer: 第76回日本血液学会総会
  • Place of Presentation: 大阪
  • Year and Date: 2014-10-31 – 2014-11-02