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Analysis of pathogenesis of refractory childhood myelodysplastic syndrome using disease-specific iPS cells

Research Project

Project/Area Number 21390308
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Pediatrics
Research InstitutionShinshu University

Principal Investigator

KOIKE Kenichi  信州大学, 医学部, 教授 (40143979)

Co-Investigator(Kenkyū-buntansha) SHIOHARA Masaaki  信州大学, 医学部, 准教授 (00293514)
坂下 一夫  信州大学, 医学部附属病院, 助教 (10345746)
Co-Investigator(Renkei-kenkyūsha) SAKASHITA Kazuo  信州大学, 医学部・附属病院, 助教 (10345746)
Project Period (FY) 2009 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥17,810,000 (Direct Cost: ¥13,700,000、Indirect Cost: ¥4,110,000)
Fiscal Year 2011: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2010: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2009: ¥7,800,000 (Direct Cost: ¥6,000,000、Indirect Cost: ¥1,800,000)
Keywords小児血液学 / 骨髄異形成症候群 / iPS細胞 / 白血病性幹細胞 / JMML / 造血幹細胞
Research Abstract

The cultured CD34-positive cells of juvenile myelomonocytic leukemia(JMML) patient were transfected the Yamanaka 4 genes, and cultured on mouse embryonic fibroblasts. Two-3 weeks later, many cell clusters with the RAS mutation were formed and negative for CD34. These cells were compatible with induced pluripotent(iPS) stem cells. We succeeded the establishment of iPS cells with myeloid differentiation potencial from the cultured JMML CD34-positive cells. We are going to elucidate pathogenesis of JMML and properties of the leukemic stem cells.

Report

(4 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • 2009 Annual Research Report
  • Research Products

    (48 results)

All 2012 2011 2010 2009 Other

All Journal Article (32 results) (of which Peer Reviewed: 32 results) Presentation (13 results) Book (3 results)

  • [Journal Article] Long-term haematological improvement after non-intensive or no chemotherapy in juvenile myelomonocytic leukaemia and poor correlation with adult myelodysplasia spliceosome-related mutations2012

    • Author(s)
      Matsuda K, Yoshida N, Miura S, Nakazawa Y, Sakashita K, Hyakuna N, Saito M, Kato F, Ogawa A, Watanabe A, Sotomatsu M, Kobayashi C, Ito T, Ishida F, Manabe A, Kojima S, Koike K
    • Journal Title

      Br J Haematol

      Volume: 157 Pages: 647-50

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Genetic evaluation of childhood acute lymphoblastic leukemia in Iraq using FTA cards2012

    • Author(s)
      Al-Kzayer LF, Sakashita K, Matsuda K, Al-Hadad SA, Al-Jadiry MF, Abed WM, Abdulkadhim JM, Al-Shujairi TA, Hasan JG, Al-Abdullah HM, Al-Ani MH, Saber PA, Inoshita T, Kamata M, Koike K
    • Journal Title

      Pediatr Blood Cancer

      Volume: 59 Issue: 3 Pages: 461-7

    • DOI

      10.1002/pbc.24055

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Critical illness polyneuropathy and myopathy caused by bacillus cereus sepsis in acute lymphoblastic leukemia2012

    • Author(s)
      Hirabayashi K, Shiohara M, Suzuki T, Saito S, Tanaka M, Yanagisawa R, Tsuruta G, Fukuyama T, Hidaka Y, Nakazawa Y, Shimizu T, Sakashita K, Koike K
    • Journal Title

      J Pediatr Hematol Oncol

      Volume: 34 Pages: 110-3

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Genetic analysis of TP53 in childhood myelodysplastic syndrome and juvenile myelomonocytic leukemia2011

    • Author(s)
      Saito S, Matsuda K, Taira C, Sano K, Tanaka-Yanagisawa M, Yanagisawa R, Nakazawa Y, Sakashita K, Shiohara M, Koike K
    • Journal Title

      Leuk Res.

      Volume: 35 Pages: 1578-84

    • NAID

      120007108235

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Retrospective analysis of risk factors for development of liver dysfunction in transient leukemia of Down syndrome2011

    • Author(s)
      Hirabayashi K, Shiohara M, Takahashi D, Saito S, Tanaka M, Yanagisawa R, Sakashita K, Nakamura T, Ishii E, Koike K
    • Journal Title

      Leuk Lymphoma

      Volume: 52 Pages: 1523-7

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Autoimmune lymphoproliferative syndrome-like disease with somatic KRAS mutation2011

    • Author(s)
      Takagi M, Shinoda K, Piao J, Mitsuiki N, Takagi M, Matsuda K, Muramatsu H, Doisaki S, Nagasawa M, Morio T, Kasahara Y, Koike K, Kojima S, Takao A, Mizutani
    • Journal Title

      Blood

      Volume: 117 Pages: 2887-90

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Engraftment syndrome, but not acute graft-versus-host disease, younger age, CYP3A5 or MDR1 polymorphisms, increases tacrolimus clearance in pediatric hematopoietic stem cell transplantation2011

    • Author(s)
      Yanagisawa R, Katsuyama Y, Shigemura T, Saito S, Tanaka M, Nakazawa Y, Sakashita K, Shiohara M, Koike K
    • Journal Title

      Bone Marrow Transplantation

      Volume: 46 Pages: 90-97

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Disappearance of minimal residual disease after the early withdrawal of immunosuppressants in a patient with juvenile myelomonocytic leukemia2011

    • Author(s)
      Yanagisawa R, Matsuda K, Sakashita K, Nakazawa Y, Tanaka M, Saito S, Yoshikawa K, Kamijo T, Shiohara M, Koike K
    • Journal Title

      Pediatr Blood Cancer

      Volume: 56 Pages: 501-2

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Genetic analysis of TP53 in childhood myelodysplastic syndrome and juvenile myelomonocytic leukemia2011

    • Author(s)
      Saito S, Matsuda K, Taira C, Sano K, Tanaka-Yanagisawa M, Yanagisawa R, Nakazawa Y, Sakashita K, Shiohara M, Koike K
    • Journal Title

      Leuk Res

      Volume: 35 Pages: 1578-84

    • NAID

      120007108235

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Disappearance of minimal residual disease after the early withdrawal of immnunosuppressants in a patient with juvenile myelomonocytic leukemia2011

    • Author(s)
      Yanagisawa R, Matsuda K, Sakashita K, Nakazawa Y, Tanaka M, Saito S, Yoshikawa K, Kamijo T, Shiohara M, Koike K
    • Journal Title

      Pediatr Blood Cancer

      Volume: 56 Issue: 3 Pages: 166-71

    • DOI

      10.1002/pbc.22849

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Autoimmune lymphoproliferative syndrome-like disease with somatic KRAS mutation.2011

    • Author(s)
      Takagi M, Matsuda K, Koike K, et, al.
    • Journal Title

      Blood

      Volume: 117 Pages: 2887-90

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Engraftment syndrome, but not acute graft-versus-host disease, younger age, CYP3A5 or MDR1 polymorphisms, increases tacrolimus clearance in pediatric hematopoietic stem cell transplantation.2011

    • Author(s)
      Yanagisawa R, Katsuyama Y, Shigemura T, Saito S, Koike K, et, al.
    • Journal Title

      Bone Marrow Transplantation

      Volume: 2011 Pages: 90-7

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Disappearance of minimal residual disease after the early withdrawal of immunosuppressants in a patient with juvenile myelomonocytic leukemia.2011

    • Author(s)
      Yanagisawa R Matsuda K, Koike K, et, al.
    • Journal Title

      Pediatr Blood Cancer

      Volume: 56 Pages: 501-2

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] HDM2 impairs Noxa transcription and affects apoptotic cell death in a p53/p73-dependent manner in neuroblastoma.2011

    • Author(s)
      Shi Y, Koike K, Kamijo T, et, al.
    • Journal Title

      Eur J Cancer

      Volume: 46 Pages: 2324-34

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Increased pretransplant QT dispersion as a risk factor for the development of cardiac complications during and after preparative conditioning for pediatric allogeneic hematopoietic stem cell transplantation2010

    • Author(s)
      Motoki N, Shimizu T, Akazawa Y, Saito S, Tanaka M, Yanagisawa R, Motoki H, Nakazawa Y, Sakashita K, Iwasaki Y, Shiohara M, Koike K
    • Journal Title

      Pediatr Transplant

      Volume: 14 Pages: 986-92

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Long-term survival after non-intensive chemotherapy in some juvenile myelomonocytic leukemia patients with CBL mutations, and the possible presence of normal individuals with the mutations2010

    • Author(s)
      Matsuda K, Taira C, Sakashita K, Saito S, Tanaka-Yanagisawa M, Yanagisawa R, Nakazawa Y, Shiohara M, Fukushima K, Oda M, Honda T, Nakahata T, Koike K
    • Journal Title

      Blood

      Volume: 115 Pages: 5429-31

    • Related Report
      2011 Final Research Report 2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mutations in the ribosomal protein genes in Japanese patients with Diamond-Blackfan Anemia2010

    • Author(s)
      Konno Y, Toki T, Tandai S, Xu G, Wang R, Terui K, Ohga S, Hara T, Hama A, Kojima S, Hasegawa D, Kosaka Y, Yanagisawa R, Koike K, Kanai R, Imai T, Hongo T, Park MJ, Sugita K, Ito E
    • Journal Title

      Haematologica

      Volume: 95 Pages: 1293-9

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Polymyxin-direct hemoperfusion for sepsisinduced multiple organ failure2010

    • Author(s)
      Hirabayashi K, Shiohara M, Saito S, Tanaka M, Yanagisawa R, Tsuruta G, Fukuyama T, Hidaka Y, Nakazawa Y, Shimizu T, Sakashita K, Koike K
    • Journal Title

      Pediatr Blood Cancer

      Volume: 55 Pages: 202-5

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Low toxicity of a conditioning with 8-Gy total body irradiation, fludarabine and cyclophosphamide as preparative regimen for allogeneic hematopoietic stem cell transplantation in pediatric hematological malignancies.Pediatric Transplantation, 2009 13: 737-45.2010

    • Author(s)
      Hirabayashi K, Shiohara M, Koike K, et, al.
    • Journal Title

      Pediatr Blood Cancer

      Volume: 55 Pages: 202-5

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Quantitative assessment of PTPN11 or RAS mutations at the neonatal period and during the clinical course in patients with juvenile myelomonocytic leukaemia2009

    • Author(s)
      Matsuda K, Sakashita K, Taira C, Tanaka-Yanagisawa M, Yanagisawa R, Shiohara M, Kanegane H, Hasegawa D, Kawasaki K, Endo M, Yajima S, Sasaki S, Kato K, Koike K, Kikuchi A, Ogawa A, Watanabe A, Sotomatsu M, Nonoyama S, Koike K
    • Journal Title

      Br J Haematol

      Volume: 141 Pages: 567-75

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Ela2 mutations and clinical manifestations in familial congenital neutropenia2009

    • Author(s)
      Shiohara M, Shigemura T, Saito S, Tanaka M, Yanagisawa R, Sakashita K, Asada H, Ishii E, Koike K, Chin M, Kobayashi M, Koike K
    • Journal Title

      J Pediatr Hematol Oncol

      Volume: 31 Pages: 319-24

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Cryptic insertion into 11q23 of MLLT10 on 10p12 not involved in t(1 ; 15 ; 11 ; 10)(p36 ; q11 ; q23 ; q24) generated MLL/MLLT10 fusion transcript in infant acute biphenotypic leukemia : application of genomic MLL rearrangement to quantification of minimal residual disease2009

    • Author(s)
      Matsuda K, Tanaka M, Araki S, Yanagisawa R, Yamauchi K, Koike K
    • Journal Title

      Cancer Genet Cytogenet.

      Volume: 190 Pages: 113-20

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Correlation of clinical features with the mutational status of GM-CSF signaling pathway-related genes in juvenile myelomonocytic leukemia2009

    • Author(s)
      Yoshida N, Yagasaki H, Xu Y, Matsuda K, Yoshimi A, Takahashi Y, Hama A, Nishio N, Muramatsu H, Watanabe N, Matsumoto K, Kato K, Ueyama J, Inada H, Goto H, Yabe M, Kudo K, Mimaya J, Kikuchi A, Manabe A, Koike K, Kojima S
    • Journal Title

      Pediatr Res

      Volume: 65 Pages: 334-40

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Low toxicity of a conditioning with 8-Gy total body irradiation, fludarabine and cyclophosphamide as preparative regimen for allogeneic hematopoietic stem cell transplantation in pediatric hematological malignancies2009

    • Author(s)
      Yanagisawa R, Nakazawa Y, Sakashita K, Tanaka M, Shikama N, Kamijo T, Shiohara M, Koike K
    • Journal Title

      Pediatric Transplantation

      Volume: 13 Pages: 737-45

    • NAID

      120007110436

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Urinary excretion of ganciclovir contributes to improvement of adenovirus-associated hemorrhagic cystitis after allogeneic bone marrow transplantation2009

    • Author(s)
      Nakazawa Y, Suzuki T, Fukuyama T, Katsuyama Y, Tanaka M, Yanagisawa R, Sakashita K, Shiohara M, Koike K
    • Journal Title

      Pediatric Transplantation

      Volume: 13 Pages: 632-5

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Quantitative assessment of PTPN11 or RAS mutations at the neonatal period and during the clinical course in patients with juvenile myelomonocytic leukaemia.2009

    • Author(s)
      Matsuda K, Sakashita K, Taira C, Tanaka-Yanagisawa M, Koike K, et al.
    • Journal Title

      Br J Haematol 141

      Pages: 567-575

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cryptic insertion into 11q23 of MLLT10 on 10p12 not involved in t (1 ; 15 ; 11 ; 10)(p36 ; q11 ; q23 ; q24) generated MLL/MLLT10 fusion transcript in infant acute biphenotypic leukemia : application of genomic MLL rearrangement to quantification of minimal residual disease.2009

    • Author(s)
      Matsuda K, Tanaka M, Koike K, et al.
    • Journal Title

      Cancer Genet Cytogenet. 190

      Pages: 113-120

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Correlation of clinical features with the mutational status of GM-CSF signaling pathway-related genes in juvenile myelomonocytic leukemia.2009

    • Author(s)
      Yoshida N, Yagasaki H, Koike K, et al.
    • Journal Title

      Pediatr Res 512

      Pages: 334-340

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Low toxicity of a conditioning with 8-Gy total body irradiation, fludarabine and cyclophosphamide as preparative regimen for allogeneic he matopoietic stem cell transplantation in pediatric hematological malignancies. Pediatric Transplantation, 2009 13 : 737-45.2009

    • Author(s)
      Yanagisawa R, Nakazawa Y, Koike K, et al.
    • Journal Title

      Pediatric Transplantation 13

      Pages: 737-745

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Telecommunication system for children undergoing stem cell transplantation

    • Author(s)
      Higuchi K, Nakazawa Y, Sakata N, Takizawa M, Ohso K, Tanaka M, Yanagisawa R, Koike K
    • Journal Title

      Pediatr Int.

      Volume: (in press)

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Long-term survival after non-intensive chemotherapy in some juvenile myelomonocytic leukemia patients with CBL mutations, and the possible presence of normal individuals with the mutations

    • Author(s)
      Matsuda K, Taira C, Sakashita K, Koike K, et al.
    • Journal Title

      Blood (in press)

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Engraftment syndrome, but not acute graft-versus-host disease, younger age, CYP3A5 or MDR1 polymorphisms, increases tacrolimus clearance in pediatric hematopoietic stem cell transplantation.

    • Author(s)
      Yanagisawa R, Katsuyama Y, Shigemura T, Saito S, Koike K, et al.
    • Journal Title

      Bone Marrow Transplantation (in press)

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Presentation] トランスポゾンを用いた慢性肉芽腫症に対する新たな遺伝子治療法の開発2012

    • Author(s)
      重村倫成、中沢洋三、松田和之、小池健一
    • Organizer
      第115回日本小児科学会学術集会
    • Place of Presentation
      福岡
    • Related Report
      2011 Final Research Report
  • [Presentation] チェルノブイリ原発事故と福島第一原発事故-人体への影響-2011

    • Author(s)
      小池健一
    • Organizer
      第53回日本小児血液・がん学会学術集会
    • Place of Presentation
      前橋
    • Related Report
      2011 Final Research Report
  • [Presentation] T細胞性悪性リンパ腫再発に対してネララビント臍帯血移植を併用した1例2011

    • Author(s)
      柳沢俊光、小池健一, 他
    • Organizer
      第53回日本小児血液・がん学会学術集会
    • Place of Presentation
      前橋
    • Related Report
      2011 Final Research Report
  • [Presentation] PiggyBacトランスポゾン法を用いて遺伝子修復したX連鎖慢性肉芽腫症患者T細胞からのiPS細胞の樹立2011

    • Author(s)
      重村倫成、中沢洋三、小池健一, 他
    • Organizer
      第53回日本小児血液・がん学会学術集会
    • Place of Presentation
      前橋
    • Related Report
      2011 Annual Research Report 2011 Final Research Report
  • [Presentation] FTA cards for genetic evaluation of childhood ALL in Iraq2011

    • Author(s)
      Al Kzayer, Sakashita K, Koike K, et al
    • Organizer
      第73回日本血液学会学術集会
    • Place of Presentation
      名古屋
    • Related Report
      2011 Final Research Report
  • [Presentation] 小児同種造血幹細胞移植後再発の予後に関する検討2011

    • Author(s)
      Sakashita K, Koike K, et al
    • Organizer
      第73回日本血液学会学術集会
    • Place of Presentation
      名古屋
    • Related Report
      2011 Final Research Report
  • [Presentation] チェルノブイリ原発事故と福島第一原発事故-人体への影響-2011

    • Author(s)
      小池健一
    • Organizer
      第53回日本小児血液・がん学会学術集会
    • Place of Presentation
      前橋(招待講演)
    • Related Report
      2011 Annual Research Report
  • [Presentation] FTA cards for genetic evaluation of childhood ALL in Iraq2011

    • Author(s)
      Al Kzayer, Sakashita K, Koike K, et al
    • Organizer
      第73回日本血液学会学術集会
    • Place of Presentation
      名古屋国際会議場
    • Related Report
      2011 Annual Research Report
  • [Presentation] 小児同種造血幹細胞移植後再発の予後に関する検討2011

    • Author(s)
      Sakashita K, Koike K, et al
    • Organizer
      第73回日本血液学会学術集会
    • Place of Presentation
      名古屋国際会議場
    • Related Report
      2011 Annual Research Report
  • [Presentation] 教育セミナー小児科領域におけるITの活用2010

    • Author(s)
      小池健一
    • Organizer
      日本小児科学会
    • Place of Presentation
      盛岡市
    • Year and Date
      2010-04-23
    • Related Report
      2010 Annual Research Report
  • [Presentation] 血液教育セッション2:若年性骨髄単球性白血病の遺伝子異常とMRD検索2009

    • Author(s)
      小池健一
    • Organizer
      日本小児血液学会
    • Year and Date
      2009-11-27
    • Related Report
      2009 Annual Research Report
  • [Presentation] 若年性骨髄単球性白血病の遺伝子異常とMRD検索2009

    • Author(s)
      小池健一、松田和之
    • Organizer
      第51回日本小児血液学会総会
    • Place of Presentation
      東京
    • Related Report
      2011 Final Research Report
  • [Presentation] 遺伝子変異特異的定量PCR法を用いた若年性骨髄単球性白血病の発症時期の検討2009

    • Author(s)
      松田和之、小池健一, 他
    • Organizer
      第71回本血液学会学術集会
    • Place of Presentation
      京都
    • Related Report
      2011 Final Research Report
  • [Book] 標本に学ぶ血液疾患症例、2種類の染色体異常を認めた若年性慢性単球性白血病-juvenile myelomonocytic leukemia(JMML)の1例2012

    • Author(s)
      小池健一、松崎聡、松田和之
    • Publisher
      医薬ジャーナル社
    • Related Report
      2011 Final Research Report
  • [Book] 標本に学ぶ血液疾患症例2012

    • Author(s)
      小池健一、松崎聡、松田和之
    • Publisher
      医薬ジャーナル社
    • Related Report
      2011 Annual Research Report
  • [Book] 血液・腫瘍科、若年性慢性骨髄単球性白血病の分子病態解明の進歩2010

    • Author(s)
      小池健一, ほか
    • Publisher
      科学評論社
    • Related Report
      2011 Final Research Report

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Published: 2009-04-01   Modified: 2016-04-21  

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