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2014 Fiscal Year Annual Research Report

小児骨髄系造血悪性腫瘍疾患におけるRAS変異体細胞モザイクの解析

Research Project

Project/Area Number 24791054
Research InstitutionNagoya University

Principal Investigator

村松 秀城  名古屋大学, 医学部附属病院, 助教 (00572570)

Project Period (FY) 2012-04-01 – 2015-03-31
Keywords若年性骨髄単球性白血病 / 体細胞モザイク / RAS
Outline of Annual Research Achievements

若年性骨髄単球性白血病(Juvenile myelomonocytic leukemia; JMML)はまれな小児特有の白血病である。JMMLの原因遺伝子として、PTPN11、NRAS、KRAS、NF1、CBLの変異が知られている。これらの遺伝子変異は体細胞変異(somatic mutation)であるが、同じ遺伝子の生殖細胞系列変異(germline mutation)がNoonan症候群(PTPN11)、cardio-faci-cutaneous(CFC)症候群(RAS)、Germline CBL症候群(CBL)などの先天性遺伝疾患の原因であることが近年相次いで明らかとなった。我々は、JMMLと診断された患者の血液細胞以外の検体(爪・毛髪・口腔粘膜)由来のDNAにおける遺伝子変異の解析を通じて、偶然にも世界初となる2例のoncogenic NRAS mutationの体細胞モザイク症例を同定した。
平成24年度にこの2症例について解析を加え、英文誌上(Doisaki S, et al., Blood 2012)で報告した。
平成24年度・25年度・26年度にも継続して新規JMML症例のgermline変異解析用検体(爪・口腔粘膜由来DNA)を収集し、サンガー法・パイロシークエンス法による解析を行い、合計6例の体細胞モザイクが疑われる症例を同定し、解析を行った。

  • Research Products

    (17 results)

All 2015 2014

All Journal Article (10 results) (of which Peer Reviewed: 10 results) Presentation (7 results) (of which Invited: 1 results)

  • [Journal Article] Germline mutation of CBL is associated with moyamoya disease in a child with juvenile myelomonocytic leukemia and Noonan syndrome-like disorder.2015

    • Author(s)
      Hyakuna N, Muramatsu H, Higa T, Chinen Y, Wang X, Kojima S.
    • Journal Title

      Pediatr Blood Cancer

      Volume: 62 Pages: 542-547

    • DOI

      10.1002/pbc.25271

    • Peer Reviewed
  • [Journal Article] Choreito formula for BK virus-associated hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation.2015

    • Author(s)
      Kawashima N, Ito Y, Sekiya Y, Narita A, Okuno Y, Muramatsu H, Irie M, Hama A, Takahashi Y, Kojima S.
    • Journal Title

      Biol Blood Marrow Transplant

      Volume: 21 Pages: 319-325

    • DOI

      10.1016/j.bbmt.2014.10.018.

    • Peer Reviewed
  • [Journal Article] Aldehyde dehydrogenase-2 polymorphism contributes to the progression of bone marrow failure in children with idiopathic aplastic anaemia.2015

    • Author(s)
      Kawashima N, Narita A, Wang X, Xu Y, Sakaguchi H, Doisaki S, Muramatsu H, Hama A, Nakanishi K, Takahashi Y, Kojima S.
    • Journal Title

      Br J Haematol.

      Volume: 168 Pages: 460-463

    • DOI

      10.1111/bjh.13122

    • Peer Reviewed
  • [Journal Article] Clinical course of juvenile myelomonocytic leukemia in the blast crisis phase treated by acute myeloid leukemia-oriented chemotherapy and allogeneic hematopoietic stem cell transplantation.2014

    • Author(s)
      Ueda S, Sakata N, Muramatsu H, Sakaguchi H, Wang X, Xu Y, Kojima S, Yamaguchi T, Higa T, Takemura T.
    • Journal Title

      Int J Hematol

      Volume: 100 Pages: 502-506

    • DOI

      10.1007/s12185-014-1638-3.

    • Peer Reviewed
  • [Journal Article] First-line treatment for severe aplastic anemia in children: bone marrow transplantation from a matched family donor versus immunosuppressive therapy.2014

    • Author(s)
      Yoshida N, Kobayashi R, Yabe H, Kosaka Y, Yagasaki H, Watanabe K, Kudo K, Morimoto A, Ohga S, Muramatsu H, Takahashi Y, Kato K, Suzuki R, Ohara A, Kojima S.
    • Journal Title

      Haematologica

      Volume: 99 Pages: 1784-1791

    • DOI

      10.3324/haematol.2014.

    • Peer Reviewed
  • [Journal Article] Peripheral blood lymphocyte telomere length as a predictor of response to immunosuppressive therapy in childhood aplastic anemia.2014

    • Author(s)
      Sakaguchi H, Nishio N, Hama A, Kawashima N, Wang X, Narita A, Doisaki S, Xu Y, Muramatsu H, Yoshida N, Takahashi Y, Kudo K, Moritake H, Nakamura K, Kobayashi R, Ito E, Yabe H, Ohga S, Ohara A, Kojima S; Japan Childhood Aplastic Anemia Study Group.
    • Journal Title

      Haematologica.

      Volume: 99 Pages: 1312-1316

    • DOI

      10.3324/haematol.2013.091165.

    • Peer Reviewed
  • [Journal Article] RUNX1 mutation associated with clonal evolution in relapsed pediatric acute myeloid leukemia with t(16;21)(p11;q22).2014

    • Author(s)
      Ismael O, Shimada A, Elmahdi S, Elshazley M, Muramatsu H, Hama A, Takahashi Y, Yamada M, Yamashita Y, Horide K, Kojima S
    • Journal Title

      Int J Hematol.

      Volume: 99 Pages: 169-174

    • DOI

      10.1007/s12185-013-1495-5.

    • Peer Reviewed
  • [Journal Article] Immunosuppressive therapy with horse anti-thymocyte globulin and cyclosporine as treatment for fulminant aplastic anemia in children.2014

    • Author(s)
      Yagasaki H, Shichino H, Ohara A, Kobayashi R, Yabe H, Ohga S, Hamamoto K, Ohtsuka Y, Shimada H, Inoue M, Muramatsu H, Takahashi Y, Kojima S.
    • Journal Title

      Ann Hematol.

      Volume: 93 Pages: 747-752

    • DOI

      10.1007/s00277-013-1984-x.

    • Peer Reviewed
  • [Journal Article] Reduced intensity conditioning in allogeneic stem cell transplantation for AML with Down syndrome.2014

    • Author(s)
      Muramatsu H, Sakaguchi H, Taga T, Tabuchi K, Adachi S, Inoue M, Kitoh T, Suminoe A, Yabe H, Azuma E, Shioda Y, Ogawa A, Kinoshita A, Kigasawa H, Osugi Y, Koike K, Kawa K, Kato K, Atsuta Y, Kudo K.
    • Journal Title

      Pediatr Blood Cancer

      Volume: 61 Pages: 925-927

    • DOI

      10.1002/pbc.24883.

    • Peer Reviewed
  • [Journal Article] Long-term outcome after immunosuppressive therapy with horse or rabbit antithymocyte globulin and cyclosporine for severe aplastic anemia in children.2014

    • Author(s)
      Jeong DC, Chung NG, Cho B, Zou Y, Ruan M, Takahashi Y, Muramatsu H, Ohara A, Kosaka Y, Yang W, Kim HK, Zhu X, Kojima S.
    • Journal Title

      Haematologica.

      Volume: 99 Pages: 664-671

    • DOI

      10.3324/haematol.2013.089268

    • Peer Reviewed
  • [Presentation] 次世代シークエンスを用いた小児血液疾患の解析2015

    • Author(s)
      村松秀城
    • Organizer
      第128回信州小児臨床談話会
    • Place of Presentation
      長野県松本市( ホテル モンターニュ)
    • Year and Date
      2015-02-14 – 2015-02-14
    • Invited
  • [Presentation] Diagnostic Efficacy of Whole-Exome Sequencing in 250 patients with Congenital Bone Marrow Failure2014

    • Author(s)
      Muramatsu H, Okuno Y, Yoshida K, Doisaki S, Hama A, Wang X, Narita A, Kawashima N, Xu Y, Sakaguchi H, Takahashi Y, Sanada M, Shiraishi Y, Chiba K, Tanaka H, Miyano S, Ogawa S, Kojima S
    • Organizer
      56th ASH Annual Meeting and Exposition
    • Place of Presentation
      San Francisco, USA
    • Year and Date
      2014-12-08 – 2014-12-08
  • [Presentation] Screening of candidate RAS pathway-related genes in juvenile myelomonocytic leukemia using CRISPR/Cas system2014

    • Author(s)
      Okuno Y, Kawashima N, Muramatsu H, Hama A, Takahashi Y, Kojima S
    • Organizer
      第56回日本小児血液・がん学会学術集会
    • Place of Presentation
      岡山県岡山市( 岡山コンベンションセンター)
    • Year and Date
      2014-11-28 – 2014-11-28
  • [Presentation] Mutational analysis of RRAS in Japanese juvenile myelomonocytic leukemia patinet2014

    • Author(s)
      Wang X, Nishikawa E, Muramatsu H, Okuno Y, Sekiya Y, Kawashima N, Xu Y, Narita A, Doisaki S, Hama A, Takahashi Y, Kojima S
    • Organizer
      第56回日本小児血液・がん学会学術集会
    • Place of Presentation
      岡山県岡山市( 岡山コンベンションセンター)
    • Year and Date
      2014-11-28 – 2014-11-28
  • [Presentation] 骨髄移植後に急性散在性脳脊髄炎をきたした若年性骨髄単球性白血病の一例2014

    • Author(s)
      西川英里、高橋義行、関屋由子、川島希、奥野友介、成田敦、土居崎小夜子、入江正寛、亀井美智、村松秀城、濱麻人、小島勢二
    • Organizer
      第56回日本小児血液・がん学会学術集会
    • Place of Presentation
      岡山県岡山市( 岡山コンベンションセンター)
    • Year and Date
      2014-11-28 – 2014-11-28
  • [Presentation] Allogeneic SCT from HLA-mismatched related/unrelated donors in children with AA2014

    • Author(s)
      村松秀城、矢部普正、小林良二、菊池陽、工藤寿子、河敬世、加藤剛二、鈴木律朗、高橋義行、稲垣二郎、井上雅美、小島勢二
    • Organizer
      第76回日本血液学会学術集会
    • Place of Presentation
      大阪府大阪市( 大阪国際会議場)
    • Year and Date
      2014-11-02 – 2014-11-02
  • [Presentation] Quantification of GM-CSF hypersensitivity and suppression by an MEK1/2 inhibitor of JMML cells2014

    • Author(s)
      川島希、関屋由子、成田敦、王希楠、土居崎小夜子、奥野友介、村松秀城、入江正寛、濱麻人、高橋義行、小島勢二
    • Organizer
      第76回日本血液学会学術集会
    • Place of Presentation
      大阪府大阪市( 大阪国際会議場)
    • Year and Date
      2014-11-01 – 2014-11-01

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Published: 2016-06-01  

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