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The pathogenesis of acute myeloid leukemia due to the CAP1 gene mutation.

Research Project

Project/Area Number 24591412
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Hematology
Research InstitutionNippon Medical School

Principal Investigator

YAMAGUCHI Hiroki  日本医科大学, 医学部, 准教授 (90297937)

Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2014: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2012: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
KeywordsCAP1 / 急性骨髄性白血病 / 遺伝子変異 / CAP1
Outline of Final Research Achievements

We screened for CAP1 mutations on 200 initial presentation cases and 30 relapsed cases with acute myeloid leukemia (AML). In initial presentation subject samples, mutations were observed in one case (missense mutation), and in relapsed subject samples, mutations were observed in 3 cases (Nonsence mutation 1case, micro-insertion 2cases).We analyzed a function of the CAP1 mutation in vitro. In wild type, localization varied from cytoplasm to mitochondria by apoptotic instruction, but mutant type did not move from cytoplasm. It was found that wild/mutant type(1:1) did not induce the apoptosis that was lower than half as compared with wild type. Also mutant type did not induce the apoptosis that was lower than 1/5 as compared with wild type.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (33 results)

All 2015 2014 2013 2012 Other

All Journal Article (7 results) (of which Peer Reviewed: 5 results,  Open Access: 2 results) Presentation (26 results) (of which Invited: 1 results)

  • [Journal Article] nhibition of S100A6 induces graft versus leukemia effects in MLL/AF4-positive ALL in human PBMC-SCID mice.2014

    • Author(s)
      Tamai.H, Miyake K, Yamaguchi H, Shimada T, Dan K, Inokuchi K.
    • Journal Title

      Bone Marrow Transplantation

      Volume: 49(5) Issue: 5 Pages: 699-703

    • DOI

      10.1038/bmt.2014.18

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Granulocyte colony-stimulating factor combined regimen in cord blood transplantation for acute myeloid leukemia: A nationwide retrospective analysis in Japan2014

    • Author(s)
      1.Konuma T, Ooi J, Uchida N, Ogawa H, Ohashi K, Kanamori H, Aotsuka N, Onishi Y, Yamaguchi H, Kozai Y, Nagamura-Inoue T, Kato K, Suzuki R, Atsuta Y, Kato S, Asano S, Takahashi S.
    • Journal Title

      Haematologica

      Volume: 99 Issue: 12 Pages: e264-e268

    • DOI

      10.3324/haematol.2014.114504

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 急性骨髄性白血病とエピジェネティクス制御関連遺伝子変異2014

    • Author(s)
      脇田知志、山口博樹
    • Journal Title

      日本臨床

      Volume: 72(6) Pages: 1026-1032

    • Related Report
      2014 Annual Research Report
  • [Journal Article] Mutations of the Epigenetics Modifying Gene (DNMT3a, TET2, IDH1/2) at Diagnosis may Induce FLT3-ITD at Relapse in de novo Acute Myeloid Leukemia.2013

    • Author(s)
      Wakita S, Yamaguchi H Omori I, Terada K, Ueda T, Manabe E, Kurosawa S, Iida S, Ibaraki T, Sato Y, Todoroki T, Hirakawa T, Ryotokuji T, Arai K, Kitano T, Mitamura Y, Kosaka F, Dan K, Inokuchi K.
    • Journal Title

      Leukemia.

      Volume: 27(5) Pages: 1044-1052

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] AML再発時におけるエピジェネティック関連遺伝子変異の意義.2013

    • Author(s)
      脇田知志, 山口博樹.
    • Journal Title

      血液内科

      Volume: 67(5) Pages: 651-661

    • NAID

      40019901763

    • Related Report
      2013 Research-status Report
  • [Journal Article] Mutations of the Epigenetics Modifying Gene (DNMT3a, TET2, IDH1/2) at Diagnosis may Induce FLT3-ITD at Relapse in de novo Acute Myeloid Leukemia2013

    • Author(s)
      Yamaguchi H, Wakita S, Omori I, et al.
    • Journal Title

      Leukemia

      Volume: 27(5) Issue: 5 Pages: 1044-1052

    • DOI

      10.1038/leu.2012.317

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] 急性骨髄性白血病の今後の展望20132013

    • Author(s)
      山口博樹
    • Journal Title

      臨床血液

      Volume: 54(1) Pages: 39-48

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] The prognostic and clinical feature of HSCT patients with chemotherapy refractory acute myeloid leukemia2015

    • Author(s)
      Keiko Fukunaga, Hiroki Yamaguchi, Yusuke Fujiwara, Shunsuke Yui, Takeshi Ryotokuji, Tsuneaki Hirakawa, Masahiro Okabe, Satoshi Wakita, Hayato Tamai, Muneo Okamoto, Kazutaka Nakayama, Koiti Inokuchi
    • Organizer
      第37回 日本造血細胞移植学会総会
    • Place of Presentation
      神戸
    • Year and Date
      2015-03-05 – 2015-03-07
    • Related Report
      2014 Annual Research Report
  • [Presentation] Decision Analysis of Allogeneic Hematopoietic Stem Cell Transplantation Versus Chemotherapy in Cytogenetically Standard-Risk Acute Myeloid Leukemia in First Complete Remission: The Impact of FLT3-ITD Profile2014

    • Author(s)
      Saiko Kurosawa, Hiroki Yamaguchi, et al.
    • Organizer
      56rd American Society of Hematology
    • Place of Presentation
      San Francisco, USA
    • Year and Date
      2014-12-06 – 2014-12-08
    • Related Report
      2014 Annual Research Report
  • [Presentation] The D816V c-kit mutation confers higher proliferation activity by JAK-STAT and Src family kinase pathways compared to N822K c-kit mutation in core-binding factor acute myeloid leukemia2014

    • Author(s)
      Ikuko Omori, Hiroki Yamaguchi, Tomoaki Kitano, Noriko Miyake, Koichi Miyake, Koiti Inokuchi
    • Organizer
      56rd American Society of Hematology
    • Place of Presentation
      San Francisco, USA
    • Year and Date
      2014-12-06 – 2014-12-08
    • Related Report
      2014 Annual Research Report
  • [Presentation] The prognostic impact of cytogenetic and genetic abnormality for the achievement of the second complete remission in adult patients with acute myeloid leukemia2014

    • Author(s)
      Keiko Fukunaga, Hiroki Yamaguchi, Satoshi Wakita, Ikuko Omori, Shunsuke Yui, Takeshi Ryotokuji, Tsuneaki Hirakawa, Kunihito Arai, Tomoaki Kitano, Fumiko Kosaka, Koiti Inokuchi
    • Organizer
      第76回日本血液学会学術集会
    • Place of Presentation
      大阪
    • Year and Date
      2014-10-31 – 2014-11-02
    • Related Report
      2014 Annual Research Report
  • [Presentation] The clinical features of PTPN11 gene mutation in Japanese patients with de novo AML2014

    • Author(s)
      Shunsuke Yui, Hiroki Yamaguchi, et al
    • Organizer
      第76回日本血液学会学術集会
    • Place of Presentation
      大阪
    • Year and Date
      2014-10-31 – 2014-11-02
    • Related Report
      2014 Annual Research Report
  • [Presentation] The clinical features and prognostic impact of acute myeloid leukemia with Epigenetics Modifying Gene mutation2014

    • Author(s)
      Anna Kobayashi, Hiroki Yamaguchi, Kensuke Usuki, Yutaka Kobayashi, Kenji Tajika, Gomi Seiji, Makoto Watanabe, Kentaro Azuma, Yuko Sato, Takahiro Todoroki, Ikuko Omori, Fukunaga Keiko, Satoshi Wakita, Tsuneaki Hirakawa, Takeshi Ryotokuji, Kunihito Arai, Tomoaki Kitano1, Fumiko Kosaka, Hayato Tamai, Koiti Inokuchi
    • Organizer
      第76回日本血液学会学術集会
    • Place of Presentation
      大阪
    • Year and Date
      2014-10-31 – 2014-11-02
    • Related Report
      2014 Annual Research Report
  • [Presentation] The clinical features and prognostic impact of de novo acute myeloid leukemia with WT1mutation2014

    • Author(s)
      Makoto Watanabe, Hiroki Yamaguchi, Kensuke Usuki, Yutaka Kobayashi, Kenji Tajika, Seiji Gomi, Anna Kobayashi, Kentaro Azuma, Yuko Sato, Takahiro Todoroki, Ikuko Omori, Fukunaga Keiko, Satoshi Wakita, Tsuneaki Hirakawa, Takeshi Ryotokuji, Kunihito Arai, Tomoaki Kitano, Fumiko Kosaka, Hayato Tamai, Koiti Inokuchi
    • Organizer
      第76回日本血液学会学術集会
    • Place of Presentation
      大阪
    • Year and Date
      2014-10-31 – 2014-11-02
    • Related Report
      2014 Annual Research Report
  • [Presentation] THE DIFFERENCE OF RCSD1-ABL1- LEUKEMOGENICITY BETWEEN EXON3 OF RCSD1/EXON 4 OF ABL1 AND EXON 2 OF RCSD1/EXON 4 OF ABL12014

    • Author(s)
      Hayato Tamai , Koichi Miyake, Hiroki Yamaguchi, Kazuo Dan, Koiti Inokuchi
    • Organizer
      19th. European Hematology Association
    • Place of Presentation
      Milan, Italy
    • Year and Date
      2014-06-12 – 2014-06-15
    • Related Report
      2014 Annual Research Report
  • [Presentation] The prognostic impact of cytogenetic and genetic abnormality for the achievement of the second complete remission in adult patients with acute myeloid leukemia after first relapse2014

    • Author(s)
      Keiko Fukunaga, Hiroki Yamaguchi, Satoshi Wakita, Ikuko Omori, Shunsuke Yui, Takeshi Ryotokuji, Tsuneaki Hirakawa, Kunihito Arai, Tomoaki Kitano, Fumiko Kosaka, Kazuo Dan, Koiti Inokuchi.
    • Organizer
      19th. European Hematology Association
    • Place of Presentation
      Milan, Italy
    • Year and Date
      2014-06-12 – 2014-06-15
    • Related Report
      2014 Annual Research Report
  • [Presentation] The prognostic impact of cytogenetic and genetic abnormality for the achievement of the second complete remission in adult patients with acute myeloid leukemia2014

    • Author(s)
      Keiko Fukunaga, Hiroki Yamaguchi, Satoshi Wakita, Ikuko Omori, Shunsuke Yui, Takeshi Ryotokuji, Tsuneaki Hirakawa, Kunihito Arai, Tomoaki Kitano, Fumiko Kosaka, Kazuo Dan, Koiti Inokuchi
    • Organizer
      The 6th JSH International Symposium
    • Place of Presentation
      浜松
    • Year and Date
      2014-05-23 – 2014-05-24
    • Related Report
      2014 Annual Research Report
  • [Presentation] Stability of gene mutation in relapsed acute myeloid leukemia.2012

    • Author(s)
      Wakita S, Yamaguchi H, Omori I, Hirakawa T, Kitano T, Arai K, Mitamura Y, Kosaka F, Inokuchi K, Dan K.
    • Organizer
      The 3rd JSH International Symposium
    • Place of Presentation
      Kawagoe
    • Related Report
      2012 Research-status Report
  • [Presentation] The clinical features and prognostic impact of DNMT3A gene mutation in Japanese patients with de novo AML2012

    • Author(s)
      Ryotokuji T, Yamaguchi H, Omori I, Hirakawa T, Wakita S, Arai K, Kitano T, Mitamura Y, Kosaka F, Shimada T, Inokuchi K, Dan K.
    • Organizer
      The 3rd JSH International Symposium
    • Place of Presentation
      Kawagoe
    • Related Report
      2012 Research-status Report
  • [Presentation] The clinical features and prognostic impact of DNMT3A gene mutation in Japanese patients with de novo AML2012

    • Author(s)
      Wakita S, Yamaguchi H, Ryotokuji T, Takeuchi J, Omori I, Hirakawa T, Kitano T, Mitamura Y, Kosaka F, Inokuchi K, Dan K.
    • Organizer
      17th congress of the European hematology Association
    • Place of Presentation
      Amsterdam, Netherlands
    • Related Report
      2012 Research-status Report
  • [Presentation] The clinical features and prognostic impact of DNMT3A gene mutation in Japanese patients with de novo AML2012

    • Author(s)
      Ryotokuji T, Yamaguchi H, Usuki K, Tajika K, Gomi S, Omori I, Sato Y, Todoroki T, Arai K, Kitano T, Mitamura Y, Kosaka F, Hirakawa T, Wakita S, Inokuchi K, Dan K.
    • Organizer
      第74回日本血液学会学術集会
    • Place of Presentation
      京都
    • Related Report
      2012 Research-status Report
  • [Presentation] The clinical features and prognostic impact of de novo acute myeloid leukemia with MLL-PTD2012

    • Author(s)
      Todoroki T, Yamaguchi H, Usuki K, Tajika K, Gomi S, Omori I, Sato Y, Arai K, Kitano T, Mitamura Y, Kosaka F, Ryotokuji T, Hirakawa T, Wakita S, Inokuchi K, Dan K
    • Organizer
      第74回日本血液学会学術集会
    • Place of Presentation
      京都
    • Related Report
      2012 Research-status Report
  • [Presentation] The clinical features and prognostic impact of de novo acute myeloid leukemia with RAS mutation2012

    • Author(s)
      Sato Y, Yamaguchi H, Usuki K, Tajika K, Gomi S, Omori I, Todoroki T, Arai K, Kitano T, Mitamura Y, Kosaka F, Ryotokuji T, Hirakawa T, Wakita S, Inokuchi K, Dan K.
    • Organizer
      第74回日本血液学会学術集会
    • Place of Presentation
      京都
    • Related Report
      2012 Research-status Report
  • [Presentation] The prognostic impact of Flt3 mutation in acute promyelocytic leukemia2012

    • Author(s)
      Hirakawa T, Yamaguchi H, Wakita S, Ryotokuji T, Kosaka F, Kitano T, Arai K, Omori I, Sato Y, Todoroki T, Dan K, Inokuchi K.
    • Organizer
      第74回日本血液学会学術集会
    • Place of Presentation
      京都
    • Related Report
      2012 Research-status Report
  • [Presentation] Comparative analysis of BHAC regimen and 3+7 regimen as induction for de novo acute myeloid leukemia2012

    • Author(s)
      Fukunaga K, Yamaguchi H, Ryotokuji T, Hirakawa T, Wakita S, Tamai H, Nakayama K, Nakamura K, Inokuchi K, Dan K.
    • Organizer
      第74回日本血液学会学術集会
    • Place of Presentation
      京都
    • Related Report
      2012 Research-status Report
  • [Presentation] エピジェネティクス制御遺伝子変異は急性骨髄性白血病の多様な遺伝子変異の出現に寄与する.

    • Author(s)
      脇田知志, 山口博樹, 了徳寺剛, 平川経晃, 大森郁子, 北野智章, 荒井邦仁, 三田村佳勇, 小坂文子, 檀 和夫, 猪口孝一.
    • Organizer
      第109回日本内科学会総会
    • Place of Presentation
      東京
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] Comprehensive gene mutation analyses in acute myeloid leukemia: overlap of the gene mutations are important for the prognosis of the intermediate risk karyotype group.

    • Author(s)
      Wakita S, Yamaguchi H, Ryotokuji T, Hirakawa T, Omori I, Kitano T, Arai K, Kosaka F, Dan K, Inokuchi K.
    • Organizer
      18th. European Hematology Association.
    • Place of Presentation
      Stockholm, Sweden
    • Related Report
      2013 Research-status Report
  • [Presentation] The prognostic impact of complex gene mutation in the intermediate risk karyotype AML.

    • Author(s)
      Wakita S, Yamaguchi H, Usuki K, Kobayashi Y, Gomi S, Tajika K, Hirakawa T, Ryotokuji T, Azuma K, Sato Y, Todoroki T, Omori I, Fukunaga K, Arai K, Kitano T, Kosaka F, Dan K, Inokuchi K.
    • Organizer
      第75回日本血液学会.
    • Place of Presentation
      札幌
    • Related Report
      2013 Research-status Report
  • [Presentation] The clinical feature and prognostic impact of de novo acute myeloid leukemia with Runx1 mutation.

    • Author(s)
      Azuma K, Yamaguchi H, Usuki K, Kobayashi Y, Tajika K, Gomi S, Sato Y, Todoroki T, Omori I, Fukunaga K, Wakita S, Hirakawa T, Ryotokuji T, Arai K, Kitano T, Kosaka F, Dan K, Inokuchi K.
    • Organizer
      第75回日本血液学会.
    • Place of Presentation
      札幌
    • Related Report
      2013 Research-status Report
  • [Presentation] The prognostic impact of additional gene mutations among intermediate risk AML with CEBPA and NPM1.

    • Author(s)
      Fukunaga K, Yamaguchi H, Wakita S, Usuki K, Kobayashi Y, Gomi S, Tajika K, Ryotokuji T, Hirakawa T, Azuma K, Sato Y, Todoroki T, Omori I, Arai K, Kitano T, Kosaka F, Dan K, Inokuchi K.
    • Organizer
      第75回日本血液学会.
    • Place of Presentation
      札幌
    • Related Report
      2013 Research-status Report
  • [Presentation] The Prognostic Impact Of Complex Gene Mutation In The Intermediate Risk Karyotype Acute Myeloid Leukemia.

    • Author(s)
      Satoshi Wakita, Hiroki Yamaguchi, Takeshi Ryotokuji, Tuneaki Hirakawa, Ikuko Omori, Tomoaki Kitano, Kunihito Arai, Yoshio Mitamura, Fumiko Kosaka, Kazuo Dan, and Koiti Inokuchi.
    • Organizer
      55rd American Society of Hematology
    • Place of Presentation
      New Orleans, LA, USA
    • Related Report
      2013 Research-status Report
  • [Presentation] 再発急性骨髄性白血病の第2寛解率に影響を与える染色体異常や遺伝子変異の探索.

    • Author(s)
      福永景子、山口博樹、了徳寺剛、平川経晃、脇田知志、荒井邦仁、北野智章、小坂文子、玉井勇人、中山一隆、猪口孝一.
    • Organizer
      第36回日本造血細胞移植学会総会
    • Place of Presentation
      沖縄
    • Related Report
      2013 Research-status Report
  • [Presentation] 移植適応を決定するうえでの遺伝子変異解析の重要性.

    • Author(s)
      脇田知志、山口博樹、了徳寺剛、平川経晃、北野智章、荒井邦仁、小坂文子、猪口孝一.
    • Organizer
      第36回日本造血細胞移植学会総会
    • Place of Presentation
      沖縄
    • Related Report
      2013 Research-status Report

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Published: 2013-05-31   Modified: 2019-07-29  

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