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CML幹細胞における細胞周期解析と新治療法開発に向けた研究

Publicly Offered Research

Project AreaDevelopment of Novel Treatment Strategies Targeting Cancer Stem Cells
Project/Area Number 23130513
Research Category

Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionKinki University

Principal Investigator

松村 到  近畿大学, 医学部, 教授 (00294083)

Project Period (FY) 2011-04-01 – 2013-03-31
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥15,340,000 (Direct Cost: ¥11,800,000、Indirect Cost: ¥3,540,000)
Fiscal Year 2012: ¥7,670,000 (Direct Cost: ¥5,900,000、Indirect Cost: ¥1,770,000)
Fiscal Year 2011: ¥7,670,000 (Direct Cost: ¥5,900,000、Indirect Cost: ¥1,770,000)
Keywords慢性骨髄性白血病 / 白血病幹細胞 / 微小残存病変 / 分子標的療法
Outline of Annual Research Achievements

本研究では、慢性骨髄性白血病(CML)の治癒を目指してCML幹細胞の生物学的・分子遺伝学的な特性や生体内動態を解明するとともに、CML幹細胞を標的とした新たな治療薬の開発することを目的とした。本年度は、CML幹細胞に特異的な表面抗原の同定を試み、CML患者の骨髄を用い、single cell PCR法による網羅的表面抗原、内的因子の発現解析を行った。
本研究への同意を得た慢性期CMLの患者10症例(診断時5例、チロシンキナーゼ阻害薬投与中5例)の骨髄から、造血幹細胞を含むCD34+38-細胞を分離、個々の細胞におけるBCR-ABLの発現を評価し、BCR-ABL陽性のCML幹細胞、BCR-ABL陰性の正常幹細胞を得た。それぞれの細胞における表面抗原CD1-350、及びBim-1などの幹細胞維持に必須の細胞内機能分子の発現を同時に解析することにより、BCR-ABL陽性細胞特異的、かつより未分化な細胞に発現する表面抗原を抽出した。その結果、CML幹細胞特異的抗原として、CD120a (receptor for both TNF-#61537; and TNF-#61538;#61481; , CD225 (IFN induced transmembrane protein 1), CD294 (binds to PGD2, Th2 activator)を同定した。診断時の骨髄を用いた検討では、これらの抗原を組み合わせて用いることによりCD34+38-細胞からBCR-ABL陽性のCML細胞を濃縮することが可能であった。また、これら分子の発現は、健常人のCD34+38-細胞において認めらないことから、これらの抗原は、生体内に残存するCML幹細胞を同定する上でのマーカーとなるだけでなく、新たな治療標的として有用である可能性が示唆された。

Research Progress Status

24年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

24年度が最終年度であるため、記入しない。

Report

(2 results)
  • 2012 Annual Research Report
  • 2011 Annual Research Report
  • Research Products

    (49 results)

All 2013 2012 2011

All Journal Article (25 results) (of which Peer Reviewed: 25 results) Presentation (20 results) Book (4 results)

  • [Journal Article] Clinical importance of human herpes virus-8 and human immunodeficiency virus infection in primary effusion lymphoma.2013

    • Author(s)
      Kumode T
    • Journal Title

      Leuk Lymphoma

      Volume: 未確定

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Localised giant haematoma and subsequent widespread purpura as a sign of acquired haemophilia A.2013

    • Author(s)
      Oiso N, Hirase C, Morita Y, Hirao A, Uchida S, Sasakawa A, Toyomasu M, Tatsumi Y, Matsumura I, Kawada A.
    • Journal Title

      Australas J Dermatol.

      Volume: 17 Issue: 3 Pages: 144-150

    • DOI

      10.1179/102453312x13376952196377

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Treatment for de novo chronic myeloid leukemia in chronic phase.2012

    • Author(s)
      Hirase C
    • Journal Title

      日本臨床

      Volume: 70 Pages: 298-303

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Pathogenesis and pathophysiology of chronic myeloid leukemia in chronic phase.2012

    • Author(s)
      Hirase C
    • Journal Title

      日本臨床

      Volume: 70 Pages: 293-297

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Sub-acute demyelinating polyradiculoneuropathy as an initial symptom of peripheral T cell lymphoma, not otherwise specified (PTCL-NOS).2012

    • Author(s)
      Kawanishi K
    • Journal Title

      Intern Med.

      Volume: 51 Pages: 2015-2020

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Localised giant haematoma and subsequent widespread purpura as a sign of acquired haemophilia A.2012

    • Author(s)
      Oiso N
    • Journal Title

      Australas J Dermatol.

      Volume: 未確定 Issue: 3 Pages: e67-e69

    • DOI

      10.1111/j.1440-0960.2012.00907.x

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Signaling through the interleukin-18 receptor α attenuates inflammation in cisplatin-induced acute kidney injury.2012

    • Author(s)
      Nozaki Y
    • Journal Title

      Kidney Int.

      Volume: 82 Issue: 8 Pages: 892-902

    • DOI

      10.1038/ki.2012.226

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The clathrin assembly protein PICALM is required for erythroid maturation and transferrin internalization in mice.2012

    • Author(s)
      鈴木 麻衣
    • Journal Title

      PLoS ONE

      Volume: 7 Issue: 2 Pages: 31854-31854

    • DOI

      10.1371/journal.pone.0031854

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Loss of genomic DNA copy numbers in the p18, p16, p27 and RB loci in blastic plasmacytoid dendritic cell neoplasm.2012

    • Author(s)
      Oiso N
    • Journal Title

      Eur J Dermatol.

      Volume: 22 Issue: 3 Pages: 393-394

    • DOI

      10.1684/ejd.2012.1663

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Diffuse large B cell lymphoma with an interfollicular pattern of proliferation shows a favourable prognosis : a study of the Osaka Lymphoma Study Group2012

    • Author(s)
      Wada N, Zaki MA, Kohara M, Ogawa H, et al.(12人中4番)
    • Journal Title

      Histopathology

      Volume: 60 Issue: 6 Pages: 924-932

    • DOI

      10.1111/j.1365-2559.2011.04161.x

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] NAD-dependent histone deacetylase, SIRT1, plays essential roles in the maintenance of hematopoietic stem cells2012

    • Author(s)
      Matsui K, et al
    • Journal Title

      Biochem Biophys Res Commun

      Volume: (in press)

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effects of tamibarotene for the treatment of adult T cell leukemia2012

    • Author(s)
      Maeda Y, et al
    • Journal Title

      Ann Hematol

      Volume: (in press)

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Increased natural killer cells and decreased CD3(+) CD8(+) CD62L(+) T cells in CML patients who sustained complete molecular remission after discontinuation of imatinib2012

    • Author(s)
      Ohyashiki K, Katagiri SI, Matsumura I, (他4名、6番目)
    • Journal Title

      Br J Haematol

      Volume: 157 Issue: 2 Pages: 254-256

    • DOI

      10.1111/j.1365-2141.2011.08939.x

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] C-terminal mutation of RUNX1 attenuates the DNA-damage repair response in hematopoietic stem cells2012

    • Author(s)
      Satoh Y, Mizuki M, Kanakura Y, et al
    • Journal Title

      Leukemia

      Volume: 26(2) Issue: 2 Pages: 303-311

    • DOI

      10.1038/leu.2011.202

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cellukar senescence induction by retinoid on adult T-cell leukemia cells2011

    • Author(s)
      Maeda Y, et al
    • Journal Title

      RETROVIROLOGY

      Volume: 8

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cytokine profiles in relapsed multiple myeloma patients undergoing febrile reactions to lenalidomide2011

    • Author(s)
      Morita Y, et al
    • Journal Title

      Int J Hematol

      Volume: 94 Pages: 583-584

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Superimposed linear graft-versus-host disease and secondary cutaneous involvement of anaplastic large cell lymphoma2011

    • Author(s)
      Oiso N, et al
    • Journal Title

      Eur J Dermatol

      Volume: 21 Pages: 636-638

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] PICOT is a molecule which binds to anamorsin2011

    • Author(s)
      Satoh Y, et al
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 408 Pages: 329-333

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Frequency of intravascular large B-cell lymphoma in Japan2011

    • Author(s)
      Chihara T, et al
    • Journal Title

      J Hematol Oncol

      Volume: 11 Pages: 14-14

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A Case of Chronic Myelomonocytic leukemia Who Developed Pericardial Effusion during Stably Controlled Leukocytosis2011

    • Author(s)
      Morita Y, et al
    • Journal Title

      INTERNAL MEDICINE

      Volume: 50 Pages: 1737-1740

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] CMLに対する第二世代チロシンキナーゼ阻害薬2011

    • Author(s)
      松村到
    • Journal Title

      臨床血液

      Volume: 52 Pages: 1610-1618

    • NAID

      10029769244

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 特発性高酸球増加症候群2011

    • Author(s)
      嶋田高広, 他
    • Journal Title

      検査と技術

      Volume: 39 Pages: 593-598

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 白血球増加症2011

    • Author(s)
      平瀬主税, 他
    • Journal Title

      診断と治療

      Volume: 99 Pages: 1132-1136

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 慢性期の慢性骨髄性白血病の治療におけるシンキナーゼ阻害薬の使い分けをどうするか?2011

    • Author(s)
      松村到
    • Journal Title

      内科

      Volume: 107 Pages: 1328-1336

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 急性白血病におけるアポトーシス抑制2011

    • Author(s)
      嶋田高広, 他
    • Journal Title

      血液内科

      Volume: 62 Pages: 151-158

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Presentation] 高リスクMDSに対する同種造血幹細胞移植前にアザシチジン投与を行った4症例の検討2013

    • Author(s)
      芹澤憲太郎
    • Organizer
      第35回 日本造血細胞移植学会総会
    • Place of Presentation
      石川県立音楽堂
    • Year and Date
      2013-03-07
    • Related Report
      2012 Annual Research Report
  • [Presentation] 難治性造血器腫瘍に対するT細胞非除去HLA不一致血縁者間造血幹細胞移植の成績単一施設の後方視的検討2013

    • Author(s)
      川西一信
    • Organizer
      第35回 日本造血細胞移植学会総会
    • Place of Presentation
      石川県立音楽堂
    • Year and Date
      2013-03-07
    • Related Report
      2012 Annual Research Report
  • [Presentation] Efficacy and safety of both 5-azacitidine and deferasirox treatment in myelodysplastic symdrome2012

    • Author(s)
      芦田隆司
    • Organizer
      第74回日本血液学会学術集会
    • Place of Presentation
      国立京都国際会館
    • Year and Date
      2012-10-19
    • Related Report
      2012 Annual Research Report
  • [Presentation] Efficacy and safety of a 5-day regimen of azacitine for patients with low-risk MDS2012

    • Author(s)
      Yasuyoshi Morita
    • Organizer
      第74回日本血液学会学術集会
    • Place of Presentation
      国立京都国際会館
    • Year and Date
      2012-10-19
    • Related Report
      2012 Annual Research Report
  • [Presentation] Richter symdrome with a long-term survival treated auto-SCT and Rituximab maintenance therapy2012

    • Author(s)
      Nozomi Yamairi
    • Organizer
      第74回日本血液学会学術集会
    • Place of Presentation
      国立京都国際会館
    • Year and Date
      2012-10-19
    • Related Report
      2012 Annual Research Report
  • [Presentation] Nilotinib in CML patients with suboptimal response to imatinib:Early results from the SENSOR study2012

    • Author(s)
      Toshihiro Miyamoto
    • Organizer
      第74回日本血液学会学術集会
    • Place of Presentation
      国立京都国際会館
    • Year and Date
      2012-10-19
    • Related Report
      2012 Annual Research Report
  • [Presentation] Idenfication and characterization of acute myeloid leukemistem cells by singlcell genexpression profile2012

    • Author(s)
      田中宏和
    • Organizer
      第10回日本臨床腫瘍学会学術集会
    • Place of Presentation
      大阪国際会議場
    • Year and Date
      2012-07-26
    • Related Report
      2012 Annual Research Report
  • [Presentation] Clinical outcome of radioimmunotherapy with ASCT (Z-LEED)for relapsed and refractory B- cell lymphoma2012

    • Author(s)
      辰巳陽一
    • Organizer
      第10回日本臨床腫瘍学会学術集会
    • Place of Presentation
      大阪国際会議場
    • Year and Date
      2012-07-26
    • Related Report
      2012 Annual Research Report
  • [Presentation] 造血器疾患に対する赤血球輸血と輸血後鉄過剰症の現状2012

    • Author(s)
      芦田隆司
    • Organizer
      第60回日本輸血・細胞治療学会
    • Place of Presentation
      福島県郡山市 ホテルハマツ
    • Year and Date
      2012-05-25
    • Related Report
      2012 Annual Research Report
  • [Presentation] 真性多血症から移行した急性赤白血病に対して非血縁者間骨髄移植が有効であった1例2012

    • Author(s)
      芹澤憲太郎, 他
    • Organizer
      第34回日本造血細胞移植学会総会
    • Place of Presentation
      大阪国際会議場
    • Year and Date
      2012-02-25
    • Related Report
      2011 Annual Research Report
  • [Presentation] 同種造血幹細胞移植前後の血清フェリチン値の移植後の予後に及ぼす影響について2012

    • Author(s)
      芦田隆司, 他
    • Organizer
      第34回日本造血細胞移植学会総会
    • Place of Presentation
      大阪国際会議場
    • Year and Date
      2012-02-25
    • Related Report
      2011 Annual Research Report
  • [Presentation] SATB1 Induces Early Lymphocyte Differentiation From Primitive Hematopoietic Progenitors2011

    • Author(s)
      Yusuke Satoh, 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] An immunological indicator for discontinuation of imatinib therapy2011

    • Author(s)
      Seiichiro Katagiri, 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] Aanalysis of iron overload in patients with transfusion-dependent hematological diseases2011

    • Author(s)
      Takashi Ashida, 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] Predictabilit inhibitors of the response to tyrosine kinase via in vitro analysis of Bcr-Abl signal2011

    • Author(s)
      Masaru Shibata, 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] Clinical outcome of radioimmunotherapy with ASCT for relapsed mantle cell lymphoma2011

    • Author(s)
      Yoichi Tatsumi, 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] Therapy-related myeloid/natural killer cell precursor acute leukemia2011

    • Author(s)
      Nozomi Yamairi, 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] Efficacy of nilotinib in the early phase after initiating imatinib treatment2011

    • Author(s)
      Masaya Kawauchi, 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] Trial of imatinib discontinuation in chronic myeloid leukemia patients2011

    • Author(s)
      Yasuhiro Maeda, 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] 眼内IL-10高値で中枢神経浸潤が判明しMTXの硝子体注入と大量点滴が奏効したびまん性大細胞リンパ腫の1例2011

    • Author(s)
      宮武淳一, 他
    • 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
  • [Book] EBM血液疾患の治療2013-20142012

    • Author(s)
      松村 到
    • Total Pages
      594
    • Publisher
      中外医学社
    • Related Report
      2012 Annual Research Report
  • [Book] 診療ガイドライン UP-TO-DATE2012-20132012

    • Author(s)
      松村 到
    • Total Pages
      765
    • Publisher
      メディカルレビュー社
    • Related Report
      2012 Annual Research Report
  • [Book] 今日の診療のためにガイドライン外来診療2011

    • Author(s)
      松村到
    • Total Pages
      602
    • Publisher
      白血病
    • Related Report
      2011 Annual Research Report
  • [Book] Annual Review血液20112011

    • Author(s)
      山口晃史, 他
    • Total Pages
      229
    • Publisher
      がん性疼痛における造血因子の役割
    • Related Report
      2011 Annual Research Report

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Published: 2011-04-06   Modified: 2018-03-28  

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