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Somatic mosaicism of RAS pathway gene mutations in pediatric myeloid malignancies

Research Project

Project/Area Number 24791054
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Pediatrics
Research InstitutionNagoya University

Principal Investigator

MURAMATSU Hideki  名古屋大学, 医学部附属病院, 助教 (00572570)

Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords若年性骨髄単球性白血病 / RAS / 体細胞モザイク / RAS / NRAS / ディープシークエンス
Outline of Final Research Achievements

Juvenile myelomonocytic leukemia (JMML) is an aggressive myeloid neoplasm of early childhood characterized by the excessive proliferation of myelomonocytic cells. Somatic mutations in PTPN11, NRAS, KRAS, NF1, or CBL, which induce deregulation of the RAS signaling pathway, are responsible for the pathogenesis of JMML. We screened mutational status of JMML patients, and reported 2 patients with somatic mosaicism of oncogenic NRAS mutation (Doisaki S, et al., Blood 2012). In total, we could identified 6 patients of JMML with somatic mosaicism of RAS pathway genes.

Report

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

    (42 results)

All 2015 2014 2013 2012 2011

All Journal Article (33 results) (of which Peer Reviewed: 33 results) Presentation (9 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 Issue: 3 Pages: 542-544

    • DOI

      10.1002/pbc.25271

    • Related Report
      2014 Annual Research Report
    • 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 Issue: 2 Pages: 319-325

    • DOI

      10.1016/j.bbmt.2014.10.018

    • Related Report
      2014 Annual Research Report
    • 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 Issue: 3 Pages: 460-463

    • DOI

      10.1111/bjh.13122

    • Related Report
      2014 Annual Research Report
    • 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 Issue: 5 Pages: 502-506

    • DOI

      10.1007/s12185-014-1638-3

    • Related Report
      2014 Annual Research Report
    • 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

    • Related Report
      2014 Annual Research Report
    • 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 Issue: 8 Pages: 1312-1316

    • DOI

      10.3324/haematol.2013.091165

    • Related Report
      2014 Annual Research Report
    • 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, Horibe K, Kojima S.
    • Journal Title

      Int J Hematol

      Volume: 99 Issue: 2 Pages: 169-174

    • DOI

      10.1007/s12185-013-1495-5

    • Related Report
      2014 Annual Research Report
    • 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 Issue: 5 Pages: 747-752

    • DOI

      10.1007/s00277-013-1984-x

    • Related Report
      2014 Annual Research Report
    • 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 Issue: 5 Pages: 925-927

    • DOI

      10.1002/pbc.24883

    • Related Report
      2014 Annual Research Report 2013 Research-status Report
    • 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 Issue: 4 Pages: 664-671

    • DOI

      10.3324/haematol.2013.089268

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Wiskott-Aldrich syndrome presenting with a clinical picture mimicking juvenile myelomonocytic leukaemia.2013

    • Author(s)
      Yoshimi A, Kamachi Y, Kojima S and et al.
    • Journal Title

      Pediatr Blood Cancer.

      Volume: 60 Issue: 5 Pages: 836-841

    • DOI

      10.1002/pbc.24359

    • Related Report
      2013 Research-status Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] The landscape of somatic mutations in Down syndrome-related myeloid disorders.2013

    • Author(s)
      Yoshida K
    • Journal Title

      Nature Genet.

      Volume: 45 Issue: 11 Pages: 1293-1200

    • DOI

      10.1038/ng.2759

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Exome sequencing identifies secondary mutations of SETBP1 and JAK3 in juvenile myelomonocytic leukemia.2013

    • Author(s)
      Sakaguchi H, Yoshida K
    • Journal Title

      Nature Genet.

      Volume: 46 Issue: 8 Pages: 937-941

    • DOI

      10.1038/ng.2698

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Somatic SETBP1 mutations in myeloid malignancies.2013

    • Author(s)
      Makishima H, Yoshida K
    • Journal Title

      Nature Genet.

      Volume: 45 Issue: 8 Pages: 942-946

    • DOI

      10.1038/ng.2696

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Spliceosomal gene mutations are frequent events in the diverse mutational spectrum of chronic myelomonocytic leukemia but largely absent in juvenile myelomonocytic leukemia.2013

    • Author(s)
      Kar SA, Jankowska A, Makishima H, Visconte V, Jerez A, Sugimoto Y, Muramatsu H, Traina F, Afable M, Guinta K, Tiu RV, Przychodzen B, Sakaguchi H, Kojima S, Sekeres MA, List AF, McDevitt MA, Maciejewski JP.
    • Journal Title

      Haematologica

      Volume: 98(1) Issue: 1 Pages: 107-113

    • DOI

      10.3324/haematol.2012.064048

    • Related Report
      2013 Research-status Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Progressive hearing loss following acquired cytomegalovirus infection in an immunocompromised child.2013

    • Author(s)
      Kato K
    • Journal Title

      Am J Otolaryngol

      Volume: 34 Issue: 1 Pages: 89-92

    • DOI

      10.1016/j.amjoto.2012.09.006

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Lack of CD4(+)CD25 (+)FOXP3 (+) regulatory T cells is associated with resistance to intravenous immunoglobulin therapy in patients with Kawasaki disease.2013

    • Author(s)
      Hirabayashi Y
    • Journal Title

      Eur J Pediatr.

      Volume: Epub

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] ACTN1 Mutations Cause Congenital Macrothrombocytopenia2013

    • Author(s)
      國島伸治、吉田健一
    • Journal Title

      Am J Hum Genet

      Volume: 92 Issue: 3 Pages: 431-438

    • DOI

      10.1016/j.ajhg.2013.01.015

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Congenital dyserythropoietic anemia type 1 with a novel mutation in the CDAN1 gene previously diagnosed as congenital hemolytic anemia.2013

    • Author(s)
      Fujino H
    • Journal Title

      Int J Hematol.

      Volume: Epub

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Correlation of CYP2C19 Phenotype With Voriconazole Plasma Concentration in Children.2013

    • Author(s)
      Narita A
    • Journal Title

      J Pediatr Hematol Oncol

      Volume: Epub

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Incidence, clinical features, and risk factors of idiopathic pneumonia syndrome followins hematopoietic stem cell transplantation in children2012

    • Author(s)
      Sakaguchi H, et al
    • Journal Title

      Pediatric blood & cancer

      Volume: 58 Issue: 5 Pages: 780-784

    • DOI

      10.1002/pbc.23298

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Molecular lesions in childhood and adult acute megakaryoblastic leukemia2012

    • Author(s)
      Hama A, Muramatsu H, Makishima H, Sugimoto Y, Szpurka H, Jasek M, O'Keefe C, Takahashi Y, Sakaguchi H, Doisaki S, Shimada A, Watanabe N, Kato K, Kojima S, Maciejewski JP.
    • Journal Title

      Br J. Haematol

      Volume: 156 Issue: 3 Pages: 316-25

    • DOI

      10.1111/j.1365-2141.2011.08948.x

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Chronic myelomonocytic leukemia and atypical chronic myeloid leukemia: novel pathogenetic lesions.2012

    • Author(s)
      Muramatsu H
    • Journal Title

      Semin Oncol

      Volume: 39 Issue: 1 Pages: 67-73

    • DOI

      10.1053/j.seminoncol.2011.11.004

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] A case report: Central nervous sys tem lesions due to Juvenile myelomonocytic leukemia progressed in a boy unde rgoing first line chemotherapy2012

    • Author(s)
      H. Fukushima, T. Fukushima, A. Hiraki, R. Suzuki, S. S. A. Mahmoud, A. Yo shimi, T. Nakao, K. Kato, C. Kobayashi, K. Koike, M. Fukasawa, Y. Morishita, S. Doisaki, H. Muramatsu, R. Sumazaki
    • Journal Title

      International Journal of Hematology

      Volume: 95 Issue: 5 Pages: 581-584

    • DOI

      10.1007/s12185-012-1046-5

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Excellent outcome of allogeneic bone marrow transplantation for Fanconi anemia using fludarabine-based reduced-intensity conditioning regimen2012

    • Author(s)
      Shimada A, Takahashi Y, Muramatsu H, Hama A, Ismael O, Narita A, Sakaguchi H, Doisaki S, Nishio N, Tanaka M, Yoshida N, Matsumoto K, Kato K, Watanabe N and Kojima S.
    • Journal Title

      Int J Hematol

      Volume: 95(6) Issue: 6 Pages: 675-679

    • DOI

      10.1007/s12185-012-1079-9

    • NAID

      10030793696

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Loss of heterozygosity in 7q myeloid disorders: clinical associations and genomic pathogenesis.2012

    • Author(s)
      Jerez A
    • Journal Title

      Blood.

      Volume: 119 Issue: 25 Pages: 6109-6117

    • DOI

      10.1182/blood-2011-12-397620

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] De novo childhood myelodysplastic/myeloproliferative disease with unique molecular characteristics.2012

    • Author(s)
      Ismael O
    • Journal Title

      Br J Haematol

      Volume: 158 Issue: 1 Pages: 129-137

    • DOI

      10.1111/j.1365-2141.2012.09140.x

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Casitas B-cell lymphoma mutation in childhood T -cell acute lymphoblastic leukemia2012

    • Author(s)
      Saito Y, Aoki Y, Muramatsu H, Makishima H, Maciejewski JP, Imaizumi M, Rikiishi T, Sasahara Y, Kure S, Niihori T, Tsuchiya S, Kojima S, Matsubara Y
    • Journal Title

      Leuk Res

      Volume: 36(8) Issue: 8 Pages: 1009-15

    • DOI

      10.1016/j.leukres.2012.04.018

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Mutation in the THPO gene is not associated with aplastic anaemia in Japanese children.2012

    • Author(s)
      Wang X
    • Journal Title

      Br J Haematol

      Volume: 158 Issue: 4 Pages: 553-555

    • DOI

      10.1111/j.1365-2141.2012.09185.x

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Mutational analysis of RNA splicing machinery components in 206 children with myeloid malignancies.2012

    • Author(s)
      Sakaguchi H
    • Journal Title

      Leuk Res

      Volume: 36 Issue: 12 Pages: e215-e217

    • DOI

      10.1016/j.leukres.2012.06.002

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Somatic mosaicism for oncogenic NRAS mutations in juvenile myelomonocytic leukemia2012

    • Author(s)
      Doisaki S, Muramatsu H, Shimada A, Takahashi Y, Mori-Ezaki M, Sato M, Kawaguchi H, Kinoshita A, Sotomatsu M, Hayashi Y, Furukawa-Hibi Y, Yamada K, Hoshino H, Kiyoi H, Yoshida N, Sakaguchi H, Narita A, Wang X, Ismael O, Xu Y, Nishio N, Tanaka M, Hama A, Koike K, Kojima S
    • Journal Title

      Blood

      Volume: 120 Issue: 7 Pages: 1485-1488

    • DOI

      10.1182/blood-2012-02-406090

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Rabbit antithymocyte globulin and cyclosporine as first-line therapy for children with acquired aplastic anemia2012

    • Author(s)
      Takahashi Y, Muramatsu H, Sakata N, Hyakuna N, Hamamoto K, Kobayashi R, Ito E, Yagasaki H, Ohara A, Kikuchi A, Morimoto A, Yabe H, Kudo K, Watanabe K, Ohga S, Kojima S
    • Journal Title

      Blood

      Volume: 121(5) Issue: 5 Pages: 862-3

    • DOI

      10.1182/blood-2012-11-465633

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Mutations profile of polycythemia vera and essential thrombocythemia among Japanese children2011

    • Author(s)
      Ismael O, et al
    • Journal Title

      Pediatric blood & cancer

      Volume: (In press) Issue: 3 Pages: 530-535

    • DOI

      10.1002/pbc.23409

    • Related Report
      2012 Research-status Report
    • 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
    • Related Report
      2014 Annual Research Report
    • 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
    • Related Report
      2014 Annual Research Report
  • [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
    • Related Report
      2014 Annual Research Report
  • [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
    • Related Report
      2014 Annual Research Report
  • [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
    • Related Report
      2014 Annual Research Report
  • [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
    • Related Report
      2014 Annual Research Report
  • [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
    • Related Report
      2014 Annual Research Report
  • [Presentation] Somatic Mosaicism of RAS Pathway Gene Mutations in Juvenile Myelomonocytic Leukemia2013

    • Author(s)
      Xinan Wang, Hideki Muramatsu, Hirotoshi Sakaguchi, Yinyan Xu, Atsushi Narita, Sayoko Doisaki, Nozomu Kawashima, Olfat Ismael, Koji Nakanishi, Asahito Hama, Yoshiyuki Takahashi, Seiji Kojima
    • Organizer
      第55回日本小児血液学会
    • Place of Presentation
      ヒルトン福岡シーホーク、福岡市
    • Related Report
      2013 Research-status Report
  • [Presentation] Whole Exome Analysis Reveals Spectrum of Gene Mutations in Juvenile Myelomonocytic Leukemia2012

    • Author(s)
      Hideki Muramatsu
    • Organizer
      54th American Society of Hematology Annual meeting
    • Place of Presentation
      Atlanta, USA
    • Related Report
      2012 Research-status Report

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

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