Analysis of adult T-cell leukemia cells using multi-color flow cytometry can detect high risk asymptomatic HTLV-1 carriers to progress into adult T-cell leukemia.

• Project/Area Number: 22591028
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Hematology
• Research Institution: The University of Tokyo
• Principal Investigator: UCHIMARU Kaoru 東京大学, 医科学研究所, 准教授 (60251203)
• Co-Investigator(Kenkyū-buntansha): WATANABE Nobukazu 東京大学, 医科学研究所, 特任准教授 (10334278)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2012: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2011: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2010: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: HTLV-1 / ATL / FACS / TSLC1 / CADM1 / CD7 / ＨＴＬＶ－１ / ＡＴＬ / ＦＡＣＳ / ＴＳＬＣ１ / ＣＡＤＭ１ / ＣＤ７ / ＣＣＲ４ / TSLC-1 / HTLV-1キャリア / リスクファター

Research Abstract

ATL cells can be detected as CADM1+/CD7- cells using multi-color fllow cytometry and this analysis is helpful for monitoring therapeutic effect for ATL. This technique can purify the cells in intermediate state of oncogensis of HTLV-1 infected cells to ATL as CADM1+/CD7dim cells. These CADM1+/CD7dim cells is detected in the peripheral blood of a part of asymptomatic carriers at high risk to develop ATL.

Research Products

• [Journal Article] Development of peripheral T-cell lymphoma not otherwise specified in an HTLV-1 carrier. (2013)
  • Author(s): Ishigaki T, Isobe M, Kobayashi S, Yuji K, Ohno N, Watanabe N, Tojo A and Uchimaru K.
  • Journal Title: Int J Heamtol. Volume: prepublished online Issue: 5 Pages: 667-672
  • DOI: 10.1007/s12185-013-1314-z
  • NAID: 10031176497
  • Peer Reviewed
• [Journal Article] The CD3 versus CD7 plot in multicolor flow cytometry reflects progression of disease stage in patients infected with HTLV-I. (2013)
  • Author(s): Kobayashi S, Tian Y, Ohno N, Yuji K, Ishigaki T, Isobe M, Ohfuchi-Tsuda M, Oyaizu N, Watanabe E, Watanabe N, Tani K, Tojo A and Uchimaru K.
  • Journal Title: PLoS One Volume: 8 Issue: 1 Pages: e53728-e53728
  • DOI: 10.1371/journal.pone.0053728
  • Peer Reviewed
• [Journal Article] Adult T-cell leukemia cells are characterized by abnormalities of Helios expression that promote T-cell growth. (2013)
  • Author(s): Asanuma S, Uchimaru K, et al.
  • Journal Title: Cancer Sci Volume: - Issue: 8 Pages: 1097-1106
  • DOI: 10.1111/cas.12181
  • Peer Reviewed
• [Journal Article] Polycomb-Mediated Loss of miR-31 Activates NIK-dependent NF-κB Pathway in Adult T-cell Leukemia and Other Cancers (2012)
  • Author(s): Yamagishi M, Uchimaru K, et al.
  • Journal Title: Cancer cell Volume: 21 Issue: 1 Pages: 121-135
  • DOI: 10.1016/j.ccr.2011.12.015
  • Peer Reviewed
• [Journal Article] Arinobu Tojo and Kaoru Uchimaru Leukemic T cells are specifically enriched in aunique CD3dimCD7low subpopulation of CD4+ T cells in acute-type adult T-cell leukemia. (2011)
  • Author(s): Yamin Tian, Seiichro Kobayashi, Nobuhiro Ohno, Masamichi Isobe, Mayuko Tsuda, Yuji Zaike, Nobukazu Watanabe, Kenzaburo Tani
  • Journal Title: Cancer Sci. Volume: 102(3) Pages: 569-577
  • Peer Reviewed
• [Journal Article] Polycomb-Mediated Loss of miR-31Activates NIK-dependent NF-κ B Pathway in Adult T-cell Leukemia and Other Cancers. (2011)
  • Author(s): Makoto Yamagishi, Kazumi Nakano, Ariko Miyake, Tadanori Yamochi, Yayoi Kagami, Akihisa, Tsutsumi, Yuka Matsuda, Aiko Sato-Otsubo, Satsuki Muto, Atae Utsunomiya, Kazunari Yamaguchi, Kaoru Uchimaru, Seishi Ogawa, and Toshiki Watanabe.
  • Journal Title: Cancer cell. Volume: 21(1) Pages: 121-135
  • Peer Reviewed
• [Journal Article] Reduced dose chemotherapy for acute promyelocytic leukaemia with adult Down syndrome (2011)
  • Author(s): Tsuda, M., Ebihara, Y., Mochizuki, S., et al.(6名2番目)
  • Journal Title: Br J Haematol Volume: 155 Issue: 1 Pages: 130-132
  • DOI: 10.1111/j.1365-2141.2011.08655.x
  • Peer Reviewed
• [Journal Article] HTLV-1キャリア対応・ATL診療の問題点 (2011)
  • Author(s): 内丸薫
  • Journal Title: 臨床血液 Volume: 52 Pages: 1432-1438
  • NAID: 10029768420
• [Journal Article] 高齢者の成人T細胞白血病・リンパ腫のマネジメント (2011)
  • Author(s): 内丸薫
  • Journal Title: 血液内科 Volume: 62 Pages: 713-720
• [Journal Article] Human T-cell leukemiavirus type I (HTLV-1) proviral load and disease progression in asymptomatic HTLV-1 carriers: a nationwide prospective study in Japan. (2010)
  • Author(s): Masako Iwanaga, Toshiki Watanabe, Atae Utsunomiya, Akihiko Okayama,Kaoru Uchimaru, Ki-Ryang Koh, Masao Ogata, Hiroshi Kikuchi, Yasuko Sagara, Kimiharu Uozumi, Manabu Mochizuki, Kunihiro Tsukasaki, Yoshio Saburi, Masaomi Yamamura, Junji Tanaka, Yukiyoshi Moriuchi, Shigeo Hino, Shimeru Kamihira, and Kazunari Yamaguchi.
  • Journal Title: Blood Volume: 116(8) Pages: 1211-9
  • Peer Reviewed
• [Journal Article] Leukemic T cells are specifically enriched in a unique CD3^<dim>CD7^<low> subpopulation of CD4^+ T cells in acute-type adult T cell leukemia. (2010)
  • Author(s): Tian A, et al.
  • Journal Title: Cancer Science Volume: 102 Pages: 569-577
  • Peer Reviewed
• [Journal Article] Human T-cell leukemia virus type I(HTLV-1)proviral load and disease progression in asy mptomatic HTLV-1 carriers : a nationwide prospective study in Japan. (2010)
  • Author(s): Iwanaga M, et al.
  • Journal Title: Blood Volume: 116 Pages: 1211-1219
  • Peer Reviewed
• [Journal Article] Adult T-cell leukemia cells are characterized by abnormalities of Helios expression that promote T-cell growth.
  • Author(s): Asanuma S, Yamagishi M, Kawanami Ka, Nakano K, Sato-Otsubo A, Muto S, Sanada M, Yamochi T, Kobayashi S, Utsunomiya A, Iwanaga M, Yamaguchi K, Uchimaru K, Ogawa S and Watanabe T.
  • Journal Title: Cancer Sci. Volume: in press.
  • Peer Reviewed
• [Presentation] CD7 vs CADM1 in FACS reflects multi-step oncogenesis of ATL and discriminates HTLV-1 infected cells. (2012)
  • Author(s): Seiichro Kobayashi et al.
  • Organizer: 第74回日本血液学会学術集会
  • Place of Presentation: 京都
  • Year and Date: 2012-10-19
• [Presentation] 患者検体を用いた CD7と TSLC1/CADM1 の FACS 解析は ATL の多 段階発癌を反映する (2012)
  • Author(s): 小林誠一郎ほか
  • Organizer: 第1回 ATLシン ポジウム
  • Place of Presentation: 東京
  • Year and Date: 2012-08-25
• [Presentation] CD3とCD7の展開によるATL細胞の同定:急性型ATLの治療反応性のモニタリングとして (2011)
  • Author(s): 大野伸広、内丸薫, 他.名古屋2011
  • Organizer: 第73回日本血液学会総会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-10-14
• [Presentation] CD3 vs CD7 plot in multi-colour FACS reflects progression of disease stage of HTLV-1 infected patients (2011)
  • Author(s): Kobayashi S, Uchimaru K, et al.
  • Organizer: 第73回日本血液学会総会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-10-14
• [Presentation] Nation-wide survey of the management of adult T-cell leukemia and HTLV-1 carrier (2011)
  • Author(s): Uchimaru K, et al.
  • Organizer: 第73回日本血液学会総会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-10-14
• [Presentation] Polycomb-Mediated Epigenetic Silencing of miR-31 Activates NF-κB Signaling in Adult T-cell Leukemia (2011)
  • Author(s): Yamagishi M, Uchimaru K, et al.
  • Organizer: 第73回日本血液学会総会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-10-14
• [Presentation] HTLV-1キャリア対応・ATL診療の問題点 (2011)
  • Author(s): 内丸薫
  • Organizer: 第73回日本血液学会総会
  • Place of Presentation: 名古屋(招待講演)
  • Year and Date: 2011-10-14
• [Presentation] Multi-color FACS用いたCD3/7展開による急性型ATLの治療反応性のモニタリング (2011)
  • Author(s): 大野伸広、内丸薫, 他
  • Organizer: 第4回HTLV-1研究会
  • Place of Presentation: 東京
  • Year and Date: 2011-09-19
• [Presentation] マルチカラーFACSにおけるCD3とCD7の展開はHTLV-1感染患者 の病期の進行を反映する (2011)
  • Author(s): 小林誠一郎ほか
  • Organizer: 第4回HTLV-1 研究会
  • Place of Presentation: 東京
  • Year and Date: 2011-09-18
• [Presentation] フローサイトメトリーによるフェノタイプ解析を用いた、急性型ATLの末梢血腫瘍細胞数の評価 (2011)
  • Author(s): 石垣知寛、内丸薫, 他東京2011 Yamagishi M, Uchimaru K, et al.
  • Organizer: 第4回HTLV-1研究会
  • Place of Presentation: 東京
  • Year and Date: 2011-09-18
• [Presentation] マルチカラーFACSにおけるCD3とCD7の展開はHTLV-1感染患者の病期の進行を反映する (2011)
  • Author(s): 小林誠一郎、内丸薫, 他大野伸広、内丸薫, 他
  • Organizer: 第4回HTLV-1研究会
  • Place of Presentation: 東京
  • Year and Date: 2011-09-18
• [Presentation] Leukemic T cells are specifically enriched in a unique CD3dimCD7low Subpopulation of CD4+ T cells in acute-type adult Tcell leuk emia. (2010)
  • Author(s): Tian Y et al.
  • Organizer: ASH annual meeting.
  • Place of Presentation: Orland, USA
  • Year and Date: 2010-12-06
• [Presentation] Leukemic T cells are specifically enriched in a unique CD3^<dim>CD7^<low> subpopulation of CD4^+ T cells in acute-type adult T cell leukemia. (2010)
  • Author(s): Tian Y, et al.
  • Organizer: ASH annual meeting
  • Place of Presentation: Orland, USA
  • Year and Date: 2010-12-06
• [Presentation] Combination of CD3 and CD7 in multi-color FACS discriminates malignant cells in ATL patients. (2010)
  • Author(s): Tian Y, et al.
  • Organizer: 第72回日本血液学会総会
  • Place of Presentation: 横浜パシフィコ
  • Year and Date: 2010-09-26
• [Presentation] HTLV-1キャリアにおけるMulti-color FACS : CD3とCD7の展開によるクローン増殖性リンパ球同定の試み (2010)
  • Author(s): 大野伸広, ほか
  • Organizer: 第72回日本血液学会総会
  • Place of Presentation: 横浜パシフィコ
  • Year and Date: 2010-09-25
• [Presentation] HTLV-1キャリア末梢血におけるMulti-color FACS : CD3とCD7の展開による異常リンパ球と発症高危険群の選別の試み (2010)
  • Author(s): 大野伸広, ほか
  • Organizer: 第3回HTLV-1研究会
  • Place of Presentation: 東京大学医科学研究所
  • Year and Date: 2010-08-29
• [Presentation] Multi-color FACS for efficient discrimination of ATL cells. (2010)
  • Author(s): Tian Y, et al.
  • Organizer: 等3回HTLV-1研究会
  • Place of Presentation: 東京大学医科学研究所
  • Year and Date: 2010-08-28
• [Presentation] ATLとの鑑別を要したATLA^+PTCL-NOSの一例. (2010)
  • Author(s): 磯部優理, ほか
  • Organizer: 第3回HTLV-1研究会
  • Place of Presentation: 東京大学医科学研究所
  • Year and Date: 2010-08-28
• [Presentation] 患者血液検体を用いたCD7とTSLC1/CADM1のFACS解析はATLの多段階発癌を反映する
  • Author(s): 小林誠一郎、内丸 薫 他.
  • Organizer: 第1回ATL シンポジウム
  • Place of Presentation: 東京
• [Presentation] TSLC1/CD7を用いた造血細胞移植後のATL細胞のモニタリング
  • Author(s): 石垣知寛、内丸 薫 他.
  • Organizer: 第5回HTLV-1研究会
  • Place of Presentation: 東京
• [Presentation] 成人T細胞白血病におけるtumor initiating cell の探索の試み
  • Author(s): 矢持忠徳、内丸 薫 他.
  • Organizer: 第5回HTLV-1研究会
  • Place of Presentation: 東京
• [Presentation] 同種造血幹細胞移植を見据えたATLの治療戦略：その後方視的解析
  • Author(s): 大野伸広、内丸 薫 他.
  • Organizer: 第5回HTLV-1研究会
  • Place of Presentation: 東京
• [Presentation] 成人T細胞白血病(ATL)における新規TIAM2変異体の同定と遺伝子発現の解析
  • Author(s): 笹島悟史、内丸 薫 他.
  • Organizer: 第5回HTLV-1研究会
  • Place of Presentation: 東京
• [Presentation] Molecular Hallmarks of Adult T cell Leukemia: miRNA, Epigenetics, and Emerging Signaling Abnormalities
  • Author(s): Makoto Yamagishi, Kaoru Uchimaru, et al.
  • Organizer: 第74回日本血液学会学術集会
  • Place of Presentation: 京都
• [Presentation] CD7 vs CADM1 in FACS reflects multi-step oncogenesis of ATL and discriminates HTLV-1 infected cells.
  • Author(s): Seiichro Kobayashi, Kaoru Uchimaru, et al.
  • Organizer: 第74回日本血液学会学術集会
  • Place of Presentation: 京都
• [Presentation] Monitoring ATL cells after allogeneic hematopoietic stem cell transplantation with CADM1 and CD7.
  • Author(s): 石垣 知寛、内丸 薫 他.
  • Organizer: 第74回日本血液学会学術集会
  • Place of Presentation: 京都
• [Presentation] CD3とCD7の展開による急性型ATL細胞の同定：治療後のCD3dimCD7(-)分画のクローナリティ解析
  • Author(s): 大野伸広、内丸 薫 他.
  • Organizer: 第74回日本血液学会学術集会
  • Place of Presentation: 京都
• [Patent(Industrial Property Rights)] 患者検体を用いた HTLV-1 キャリア、成人 T 細胞白血病の発癌過程進行度又 は悪性度の評価法 (2013)
  • Inventor(s): 内丸 薫、小林誠一郎、渡辺信和
  • Industrial Property Rights Holder: 東京大学
  • Industrial Property Number: 2013-034326
  • Filing Date: 2013-02-25
  • Overseas
• [Patent(Industrial Property Rights)] 患者検体を用いたHTLV-1キャリア、成人T細胞白血病の発癌過程進行度又は悪性度の評価法 (2013)
  • Inventor(s): 内丸 薫、小林誠一郎、渡辺信和
  • Industrial Property Rights Holder: 東京大学
  • Industrial Property Rights Type: 特許
  • Filing Date: 2013-02-25