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Genetic abnormalities in acute myeloid leukemia at relapse

Research Project

Project/Area Number 26461431
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Hematology
Research InstitutionSaitama Medical University

Principal Investigator

Asou Norio  埼玉医科大学, 医学部, 教授 (50175171)

Research Collaborator MISHIMA Masayo  
FUJINAMI Miki  
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2014: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywords急性骨髄性白血病 / 再発 / 遺伝子変異 / サブクローン / 単一細胞PCR
Outline of Final Research Achievements

Gene mutations in patients with acute myeloid leukemia (AML) at initial diagnosis and relapse were examined. Mutations in the NPM1, FLT3, CEBPA, IDH1, IDH2, DNMT3A, WT1 and TP53 genes, that were frequently identified in AML patients, were mainly analyzed. Most AML patients with NPM1 mutation concomitantly had DNMT3A, FLT3, IDH1 or IDH2 mutation. Some gene mutations were withdrawn and others were acquired at relapse. In pair samples at diagnosis and relapse, it is analyzing whether an acquired gene mutation at relapse presents as a minor subclone at initial diagnosis by using whole exon sequencing and single cell PCR. These sequential molecular studies may yield valuable insights into the mechanism of leukemic recurrence.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (25 results)

All 2017 2016 2015 2014 Other

All Int'l Joint Research (1 results) Journal Article (12 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 12 results,  Acknowledgement Compliant: 4 results,  Open Access: 1 results) Presentation (12 results) (of which Int'l Joint Research: 3 results,  Invited: 1 results)

  • [Int'l Joint Research] Barts Cancer Institute(United Kingdom)

    • Related Report
      2015 Research-status Report
  • [Journal Article] Incidences and outcomes of therapy-related chronic myeloid leukemia in the era of tyrosine kinase inhibitors: Surveillance of the CML Cooperative Study Group.2017

    • Author(s)
      Iriyama N, Tokuhira M, Takaku T, Sato E, Ishikawa M, Nakazato T, Sugimoto KJ, Fujita H, Fujioka I, Hatta Y, Kizaki M, Komatsu N, Asou N, Kawaguchi T.
    • Journal Title

      Leuk Res.

      Volume: 54 Pages: 55-58

    • DOI

      10.1016/j.leukres.2017.01.003

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Diagnostic performance of procalcitonin, presepsin, and C-reactive protein in patients with hematological malignancies.2017

    • Author(s)
      Ebihara Y, Kobayashi K, Ishida A, Maeda T, Takahashi N, Taji Y, Asou N, Ikebuchi K.
    • Journal Title

      J Clin Lab Anal.

      Volume: in press Issue: 6

    • DOI

      10.1002/jcla.22147

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Frequent somatic mutations in epigenetic regulators in newly diagnosed chronic myeloid leukemia.2017

    • Author(s)
      Togasaki E, Takeda J, Yoshida K, Shiozawa Y, Takeuchi M, Kiyoi H, Ohnishi K, Ohtake S, Asou N, Kobayashi Y, Miyazaki Y, Miyano S, Ogawa S, Matsumura I, Nakaseko C, Naoe T.
    • Journal Title

      Blood Cancer J.

      Volume: 7 Issue: 4 Pages: 2017-2017

    • DOI

      10.1038/bcj.2017.36

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Lineage switch with t(6;11)(q27;q23) from T-cell lymphoblastic lymphoma to acute monoblastic leukemia at relapse.2016

    • Author(s)
      Higuchi Y, Tokunaga K, Watanabe Y, Kawakita T, Harada N, Yamaguchi S, Nosaka K, Mitsuya H, Asou N.
    • Journal Title

      Cancer Genet

      Volume: 209 Issue: 6 Pages: 267-271

    • DOI

      10.1016/j.cancergen.2016.05.070

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Unrelated bone marrow transplantation or immediate umbilical cord blood transplantation for patients with acute myeloid leukemia in first complete remission2016

    • Author(s)
      Yanada, M., Kanda, J., Ohtake, S., Fukuda, T., Sakamaki, H., Miyamura, K., Miyawaki, S., Uchida, N., Maeda, T., Nagamura-Inoue, T., Asou, N., Morishima, Y., Atsuta, Y., Miyazaki, Y., Kimura, F., Kobayashi, Y., Takami, A., Naoe, T. and Kanda, Y
    • Journal Title

      Eur J Haematol

      Volume: NA Issue: 3 Pages: 278-287

    • DOI

      10.1111/ejh.12723

    • Related Report
      2016 Annual Research Report 2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Proposal of criteria for dyserythropoiesis in the diagnosis of myelodysplastic syndromes.2016

    • Author(s)
      Kawai N, Matsuda A, Jinnai I, Ichimura T, Kayano H, Okamura D, Ishikawa M, Maeda T, Hata T, Miyazaki Y, Asou N, Bessho M, Tomonaga M.
    • Journal Title

      Int J Hematol

      Volume: 103 Issue: 2 Pages: 227-233

    • DOI

      10.1007/s12185-015-1916-8

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Lenalidomide in relapsed adult T-cell leukaemia-lymphoma or peripheral T-cell lymphoma (ATLL-001): a phase 1, multicentre, dose-escalation study.2016

    • Author(s)
      Ogura M, Imaizumi Y, Uike N, Asou N, Utsunomiya A, Uchida T, Aoki T, Tsukasaki K, Taguchi J, Choi I, Maruyama D, Nosaka K, Chen N, Midorikawa S, Ohtsu T, Tobinai K.
    • Journal Title

      Lancet Haematol

      Volume: 3 Issue: 3 Pages: e107-e118

    • DOI

      10.1016/s2352-3026(15)00284-7

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Disease evolution and outcomes in familial AML with germline CEBPA mutations.2015

    • Author(s)
      Tawana K, Wang J, Renneville A, Hills R, Loveday C, Savic A, Van Delft FW, Treleaven J, Georgiades P, Uglow E, Asou N, Uike N, Debeljak M, Jazbec J, Ancliff P, Gale R, Thomas X, Mialou V, Döhner K, Bullinger L, Preudhomme C, Chelala C, Cavenagh J, Fitzgibbon J, et al.
    • Journal Title

      Blood

      Volume: 126 Issue: 10 Pages: 1214-1223

    • DOI

      10.1182/blood-2015-05-647172

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] IDH1 and IDH2 mutations confer an adverse effect in patients with acute myeloid leukemia lacking the NPM1 mutation.2014

    • Author(s)
      Yamaguchi S, Iwanaga E, Tokunaga K, Nanri T, Shimomura T, Suzushima H, Mitsuya H, Asou N.
    • Journal Title

      Eur J Haematol

      Volume: in press Issue: 6 Pages: 471-477

    • DOI

      10.1111/ejh.12271

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Comprehensive analysis of genetic alterations and their prognostic impacts in adult acute myeloid leukemia patients2014

    • Author(s)
      Kihara R, S. Ogawa, S. (32/33) Naoe, T.
    • Journal Title

      Leukemia

      Volume: inpress Issue: 8 Pages: 1586-95

    • DOI

      10.1038/leu.2014.55

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Hematologic improvements in a myelodysplastic syndromes with myelofibrosis (MDS-F) patient treated with azacitidine.2014

    • Author(s)
      Okamura D, Matsuda A, Ishikawa M, Maeda T, Tanae K, Kohri M, Takahashi N, Kawai N, Asou N, Bessho M.
    • Journal Title

      Leuk Res Rep

      Volume: 3 Issue: 1 Pages: 24-27

    • DOI

      10.1016/j.lrr.2014.03.002

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Tamibarotene As Maintenance Therapy for Acute Promyelocytic Leukemia: Results From a Randomized Controlled Trial.2014

    • Author(s)
      Shinagawa K, Yanada M, Sakura T, Ueda Y, Sawa M, Miyatake J, Dobashi N, Kojima M, Hatta Y, Emi N, Tamaki S, Gomyo H, Yamazaki E, Fujimaki K, Asou N, Matsuo K, Ohtake S, Miyazaki Y, Ohnishi K, Kobayashi Y, Naoe T.
    • Journal Title

      J Clin Oncol.

      Volume: 32 Issue: 33 Pages: 3729-3735

    • DOI

      10.1200/jco.2013.53.3570

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Presentation] APL harboring the PML-RARA fusion gene detected by RT-PCR, which was negative by FISH analysis.2016

    • Author(s)
      佐伯豪士、岡村大輔、石川真穂、前田智也、川井信孝、松田晃、麻生範雄
    • Organizer
      第78回日本血液学会学術集会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市西区)
    • Year and Date
      2016-10-14
    • Related Report
      2016 Annual Research Report
  • [Presentation] 3’UTR methylation of the CEBPA gene in acute myeloid leukemia.2016

    • Author(s)
      木村由起子、徳永賢治、松野直史、麻生範雄、川口辰哉、岩永栄作
    • Organizer
      第78回日本血液学会学術集会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市西区)
    • Year and Date
      2016-10-14
    • Related Report
      2016 Annual Research Report
  • [Presentation] AMLの層別化治療2016

    • Author(s)
      麻生範雄
    • Organizer
      第78回日本血液学会学術集会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市西区)
    • Year and Date
      2016-10-13
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Landscape of MDS genomes as revealed by whole genome sequencing.2016

    • Author(s)
      南谷泰仁、吉田健一、片岡圭亮、永田安伸、吉里哲一、木口亨、土橋史明、臼杵憲祐、直江知樹、清井仁、千葉滋、麻生範雄、宮崎泰司、田中洋子、千葉健一、白石友一、宮野悟、小川誠司
    • Organizer
      第78回日本血液学会学術集会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市西区)
    • Year and Date
      2016-10-13
    • Related Report
      2016 Annual Research Report
  • [Presentation] Genetic Predispositions to Myeloid Neoplasms Caused By Germline DDX41 Mutations.2015

    • Author(s)
      Takeda J, Yoshida K, Makishima H, Yoshizato T, Shiozawa Y, Shiraishi Y, Okuno Y, Kon A, Nagata Y, Kataoka K, Chiba K, Tanaka H, Sanada M, Sakata-Yanagimoto M, Obara N, Nakamaki T, Ishiyama K, Haigaishi A, Chiba S, Mori H, Asou N, Kiyoi H, Miyazaki Y, Naoe T, Kubo M, Polprasert C, Maciejewski JP, Ogawa S, et al.
    • Organizer
      57th ASH Annual Meeting & Exposition
    • Place of Presentation
      Orange Country Convention Center, Orlando, U.S.A
    • Year and Date
      2015-12-05
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] WT1 mRNA levels in peripheral blood may be a predictive marker on response to azacitidine in MDS.2015

    • Author(s)
      Maeda T, Matsuda A, Okamura D, Ishakawa M, Kohri M, Takahashi N, Niitsu N, Kawai N, Asou N, Bessho M.
    • Organizer
      第77回日本血液学会学術集会
    • Place of Presentation
      石川県立音楽堂他、金沢市、石川県
    • Year and Date
      2015-10-16
    • Related Report
      2015 Research-status Report
  • [Presentation] Succesful treatment with dasatinib and chemotherapy for an ALL harboring a rare e14a3 BCR-ABL.2015

    • Author(s)
      Ishikawa M, Okamura D, Maeda T, Kawai N, Matsuda A, Minauchi K, Imai K, Asou N.
    • Organizer
      第77回日本血液学会学術集会
    • Place of Presentation
      石川県立音楽堂他、金沢市、石川県
    • Year and Date
      2015-10-16
    • Related Report
      2015 Research-status Report
  • [Presentation] Relatonship between morphological features and gene mutations in de novo AML.2015

    • Author(s)
      Kamijo R, Itonaga H, Kihara R, Nagata Y, Hata T, Asou N, Ohatake S, Ogawa S, Naoe T, Kiyoi H, Miyazaki Y.
    • Organizer
      第77回日本血液学会学術集会
    • Place of Presentation
      石川県立音楽堂他、金沢市、石川県
    • Year and Date
      2015-10-16
    • Related Report
      2015 Research-status Report
  • [Presentation] Predicitive impact of baseline WT1 mRNA expression level in peripheral blood on response to azacitidine in MDS patients.2015

    • Author(s)
      Maeda T, Matsuda A, Okamura D, Ishikawa M, Kohri M, Takahashi N, Niitsu N, Kawai N, Asou N, Bessho M.
    • Organizer
      The 6th JSH International Symposium 2015
    • Place of Presentation
      軽井沢プリンスホテルウエスト、軽井沢町、長野県
    • Year and Date
      2015-05-22
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Morphologic analysis to create suitable criteris for dyserythropoiesis in the diagnosis of myelodysplastic syndromes.2015

    • Author(s)
      Kawai N, Matsuda A, Jinnai I, Ichimura T, Kayano H, Okamura D, Ishikawa M, Maeda T, Hata T, Miyazaki Y, Asou N, Bessho M, Tomonaga M.
    • Organizer
      The 6th JSH International Symposium 2015
    • Place of Presentation
      軽井沢プリンスホテルウエスト、軽井沢町、長野県
    • Year and Date
      2015-05-22
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Prognostic Impact of Chromosomal Variation in Patients with Acute Promyelocytic Leukemia (APL); Analysis of 775 Cases Enrolled in the Japan Adult Leukemia Study Group APL Studies.2014

    • Author(s)
      Adachi M, Takeshita A, Taki T, Ohtake S, Shinagawa K, Kiyoi H, Matsuda M, Takahashi M, Emi N, Kobayashi Y, Miyamura K, Fujita H, Sakura T, Iwanaga M, Usui N, Miyawaki S, Asou N, Ohnishi K, Miyazaki Y, Naoe T.
    • Organizer
      56th ASH Annual Meeting and Exposition.
    • Place of Presentation
      Moscone Center, San Francisco, CA, U.S.A.
    • Year and Date
      2014-12-06 – 2014-12-09
    • Related Report
      2014 Research-status Report
  • [Presentation] Alterations of TP53, CREBBP and EED genes in adult patients with acute lymphoblastic leukemia.2014

    • Author(s)
      Tokunaga K, Yamaguchi S, Shimomura T, Suzushima H, Mitsuya H, Asou N.
    • Organizer
      The 76th Annual Meeting of the Japanese Society of Hematology.
    • Place of Presentation
      大阪国際会議場、大阪
    • Year and Date
      2014-10-31 – 2014-11-02
    • Related Report
      2014 Research-status Report

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Published: 2014-04-04   Modified: 2018-03-22  

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