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Development of a methylation analysis method for juvenile myelomonocytic leukemia using next-generation sequencing

Research Project

Project/Area Number 18K07816
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 52050:Embryonic medicine and pediatrics-related
Research InstitutionNagoya University

Principal Investigator

Muramatsu Hideki  名古屋大学, 医学部附属病院, 講師 (00572570)

Co-Investigator(Kenkyū-buntansha) 奥野 友介  名古屋大学, 医学部附属病院, 病院講師 (00725533)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords若年性骨髄単球性白血病 / 遺伝子メチル化 / DNAメチル化 / 小児血液学
Outline of Final Research Achievements

Juvenile myelomonocytic leukemia (JMML) is a pediatric myeloproliferative disease with a poor prognosis. We have constructed an international methylation classification using Illumina's 450k methylation array, but development of a lower-cost, high-throughput test method is required for implementation in actual clinical practice. In this study, we performed methylation analysis using the digital restriction enzyme analysis of methylation (DREAM) method, which combines two restriction enzymes that distinguish the presence or absence of methylation with next-generation sequencing technology. The DREAM method reproduces the results of the 450k methylation array with high accuracy, and has been established as a clinical test method for JMML.

Translated with www.DeepL.com/Translator (free version)

Academic Significance and Societal Importance of the Research Achievements

現在でも治療が難しいまれな小児白血病である、若年性骨髄単球性白血病(JMML)は、その治療方法を決めるためにメチル化アレイという方法による「遺伝子のメチル化」の評価が重要であることが、最近明らかとなりました。しかしながら、実際に患者さんのために遺伝子のメチル化の情報を利用するためには、より安価かつ迅速に結果が得られる方法で、JMML患者さんのメチル化評価をすることが必要です。今回の研究では、DREAM法という遺伝子を切断する制限酵素と次世代シーケンサーを組み合わせた方法を用いることで、メチル化アレイと同等の検査結果が得られることを明らかにすることができました。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (20 results)

All 2020 2019 2018 Other

All Int'l Joint Research (2 results) Journal Article (9 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 9 results,  Open Access: 8 results) Presentation (9 results) (of which Int'l Joint Research: 6 results,  Invited: 2 results)

  • [Int'l Joint Research] University of California, San Francisco(米国)

    • Related Report
      2020 Annual Research Report
  • [Int'l Joint Research] German Cancer Research Center (DKFZ)(ドイツ)

    • Related Report
      2020 Annual Research Report
  • [Journal Article] International Consensus Definition of DNA Methylation Subgroups in Juvenile Myelomonocytic Leukemia2020

    • Author(s)
      Schoenung Maximilian、Meyer Julia、Noellke Peter、Olshen Adam B.、Hartmann Mark、Murakami Norihiro、Wakamatsu Manabu、Okuno Yusuke、Plass Christoph、Loh Mignon L.、Niemeyer Charlotte M.、Muramatsu Hideki、Flotho Christian、Stieglitz Elliot、Lipka Daniel B.
    • Journal Title

      Clinical Cancer Research

      Volume: 27 Issue: 1 Pages: 158-168

    • DOI

      10.1158/1078-0432.ccr-20-3184

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Detection of subclonal SETBP1 and JAK3 mutations in juvenile myelomonocytic leukemia using droplet digital PCR2020

    • Author(s)
      Wakamatsu Manabu、Okuno Yusuke、Murakami Norihiro、Miwata Shunsuke、Kitazawa Hironobu、Narita Kotaro、Kataoka Shinsuke、Ichikawa Daisuke、Hamada Motoharu、Taniguchi Rieko、Suzuki Kyogo、Kawashima Nozomu、Nishikawa Eri、Narita Atsushi、Nishio Nobuhiro、Kojima Seiji、Muramatsu Hideki、Takahashi Yoshiyuki
    • Journal Title

      Leukemia

      Volume: 35 Issue: 1 Pages: 259-263

    • DOI

      10.1038/s41375-020-0817-x

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Essential role of PTPN11 mutation in enhanced haematopoietic differentiation potential of induced pluripotent stem cells of juvenile myelomonocytic leukaemia.2019

    • Author(s)
      Shigemura T, Matsuda K, Kurata T, Sakashita K, Okuno Y, Muramatsu H, Yue F, Ebihara Y, Tsuji K, Sasaki K, Nakahata T, Nakazawa Y, Koike K
    • Journal Title

      Br J Haematol

      Volume: 187 Issue: 2 Pages: 163-173

    • DOI

      10.1111/bjh.16060

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Successful hematopoietic stem cell transplantation from an HLA-mismatched parent for engraftment failure after unrelated cord blood transplantation in patients with juvenile myelomonocytic leukemia: Report of two cases2019

    • Author(s)
      Akahane Koshi、Watanabe Atsushi、Furuichi Yoshiyuki、Somazu Shinpei、Oshiro Hiroko、Goi Kumiko、Sakashita Kazuo、Muramatsu Hideki、Hama Asahito、Takahashi Yoshiyuki、Koike Kenichi、Kojima Seiji、Sugita Kanji、Inukai Takeshi
    • Journal Title

      Pediatric Transplantation

      Volume: なし Issue: 3

    • DOI

      10.1111/petr.13378

    • Related Report
      2019 Research-status Report 2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Defective Epstein-Barr virus in chronic active infection and haematological malignancy.2019

    • Author(s)
      Okuno Y, Murata T, Sato Y,Yoshida K, Sawada A, Inoue M, Kawa K, Seto M, Ohshima K, Shiraishi Y, Chiba K, Tanaka H, Miyano S, Nishida T, Kiyoi H, Kato S, Nakamura S, Morishima S, Yoshikawa T, Fujiwara S, Shimizu N, Isobe Y, Noguchi M, Kikuta A, Iwatsuki K, Takahashi Y, Kojima S, Ogawa S, Kimura H.
    • Journal Title

      Nat Microbiol.

      Volume: 4 Issue: 3 Pages: 404-413

    • DOI

      10.1038/s41564-018-0334-0

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Integrated molecular profiling of juvenile myelomonocytic leukemia2018

    • Author(s)
      Murakami N, Okuno Y, Yoshida K, Shiraishi Y, Nagae G, Suzuki K, Narita A, Sakaguchi H, Kawashima N, Wang X, Xu Y, Chiba K, Tanaka H, Hama A, Sanada M, Ito M, Hirayama M, Watanabe A, Ueno T, Kojima S, Aburatani H, Mano H, Miyano S, Ogawa S, Takahashi Y, Muramatsu H
    • Journal Title

      Blood

      Volume: 131 Issue: 14 Pages: 1576-1586

    • DOI

      10.1182/blood-2017-07-798157

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Comparison of conditioning regimens for autologous stem cell transplantation in children with acute myeloid leukemia: A nationwide retrospective study in Japan2018

    • Author(s)
      Sakaguchi Hirotoshi、Muramatsu Hideki、Hasegawa Daiichiro、Kudo Kazuko、Ishida Hiroyuki、Yoshida Nao、Koh Katsuyoshi、Noguchi Maiko、Shiba Norio、Tokimasa Sadao、Fukuda Takhiro、Goto Hiroaki、Miyamura Takako、Nakazawa Yozo、Hashii Yoshiko、Inoue Masami、Atsuta Yoshiko、et al
    • Journal Title

      Pediatric Blood & Cancer

      Volume: 66 Issue: 1

    • DOI

      10.1002/pbc.27459

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Sequential use of second-generation tyrosine kinase inhibitors following imatinib therapy in pediatric chronic myeloid leukemia: A report from the Japanese Pediatric Leukemia/Lymphoma Study Group2018

    • Author(s)
      Kurosawa Hidemitsu、Tanizawa Akihiko、Muramatsu Hideki、Tono Chikako、Watanabe Akihiro、Shima Haruko、Ito Masaki、Yuza Yuki、Hamamoto Kazuko、Hotta Noriko、Okada Masahiko、Saito Akiko Moriya、Manabe Atsushi、Mizutani Shuki、Adachi Souichi、Horibe Keizo、Ishii Eiichi、Shimada Hiroyuki
    • Journal Title

      Pediatric Blood & Cancer

      Volume: 65 Issue: 12

    • DOI

      10.1002/pbc.27368

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Sudden Intracranial Hemorrhage in a Patient With Atypical Chronic Myeloid Leukemia in Chronic Phase2018

    • Author(s)
      Kouzuki Kagehiro、Umeda Katsutsugu、Saida Satoshi、Kato Itaru、Hiramatsu Hidefumi、Funaki Takeshi、Kanda Kenji、Muramatsu Hideki、Yoshida Kenichi、Ogawa Seishi、Adachi Souichi
    • Journal Title

      Journal of Pediatric Hematology/Oncology

      Volume: 40 Issue: 8 Pages: e553-e556

    • DOI

      10.1097/mph.0000000000001061

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Detection of Subclonal SETBP1 and JAK3 Mutations in Patients with Juvenile Myelomonocytic Leukemia Using Droplet Digital PCR2019

    • Author(s)
      Manabu Wakamatsu, Norihiro Murakami, Yusuke Okuno, Nobuhiro Kitazawa, Hideki Muramatsu, Seiji Kojima, Yoshiyuki Takahashi
    • Organizer
      The 10th JSH International Symposium 2019
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Integrated molecular profiling of juvenile myelomonocytic leukemia2019

    • Author(s)
      Hideki Muramatsu
    • Organizer
      The 29th Symposium of the International Association for Comparative Research on Leukemia and Related Diseases (IACRLRD 2019)
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] droplet digital PCRを用いた若年性骨髄単球性白血病におけるサブクローナルなSETBP1とJAK3変異の検出2019

    • Author(s)
      若松学、村上典寛、奥野友介、北澤宏展、山森彩子、今屋雅之、吉田太郎、三輪田俊介、成田幸太郎、北澤展典、濱田太立、市川大輔、谷口理恵子、西川英里、川島希、成田敦、 西尾信博、村松秀城、小島勢二、髙橋義行
    • Organizer
      第277回日本小児科学会東海地方会
    • Related Report
      2019 Research-status Report
  • [Presentation] Detection of subclonal SETBP1 and JAK3 mutations in patients with juvenile myelomonocytic leukemia using droplet digital PCR2019

    • Author(s)
      Manabu Wakamatsu, Norihiro Murakami, Yusuke Okuno, Nobuhiro Kitazawa, Hideki Muramatsu, Seiji Kojima, Yoshiyuki Takahashi
    • Organizer
      61th American Society of Hematology Annual Meeting & Exposition
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Comprehensive Mutational Analysis of Juvenile Myelomonocytic Leukemia using Whole-genome Sequencing2019

    • Author(s)
      Yusuke Okuno, Hideki Muramatsu, Norihiro Murakami, Nozomu Kawashima, Manabu Wakamatsu, Hironobu Kitazawa, Tomoo Ogi, Yoshiyuki Takahashi
    • Organizer
      61th American Society of Hematology Annual Meeting & Exposition
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Genome-wide Methylation Analysis using the Digital Restriction Enzyme Analysis of Methylation for Stratification of Patients with Juvenile Myelomonocytic Leukemia2019

    • Author(s)
      Hironobu Kitazawa, Hideki Muramatsu, Norihiro Murakami, Yusuke Okuno, Manabu Wakamatsu, Taro Yoshida, Masayuki Imaya, Ayako Yamamori, Shunsuke Miwata, Kotaro Narita, Motoharu Hamada, Daisuke Ichikawa, Rieko Taniguchi, Nozomu Kawashima, Eri Nishikawa, Atsushi Narita, Nobuhiro Nishio, Seiji Kojima, Yoshiyuki Takahashi
    • Organizer
      61th American Society of Hematology Annual Meeting & Exposition
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Integrated molecular profiling of juvenile myelomonocytic leukemia.2018

    • Author(s)
      Muramatsu H.
    • Organizer
      The 6th TSH International Symposium
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] Integrated molecular profiling of juvenile myelomonocytic leukemia.2018

    • Author(s)
      Murakami N, Okuno Y, Yoshida K, Shiraishi Y, Nagae G, Suzuki K, Narita A, Sakaguchi H, Kawashima N, Wang X, Xu Y, Chiba K, Tanaka H, Hama A, Sanada M, Ito M, Hirayama M, Watanabe A, Ueno T, Kojima S, Aburatani H, Mano H, Miyano S, Ogawa S, Takahashi Y, Muramatsu H.
    • Organizer
      第9回日本血液学会国際シンポジウム
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] DREAM法を用いた若年性骨髄単球性白血病に対するメチル化解析2018

    • Author(s)
      北澤宏展, 村上典寛, 奥野友介, 村松秀城, 若松 学, 三輪田俊介, 成田幸太郎 ,片岡伸介, 濱田太立, 市川大輔, 谷口理恵子, 鈴木喬悟, 川島 希, 西川英里, 成田 敦, 西尾信博, 小島勢二, 高橋義
    • Organizer
      第60回日本小児血液・がん学会学術集会
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2022-01-27  

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