Extraction of an intermediate state between the healthy HTLV-1 carrier and indolent ATL.

• Project/Area Number: 23591394
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: National Center of Neurology and Psychiatry (2012-2013); Nagasaki University (2011)
• Principal Investigator: TSUKASAKI KUNIHIRO 独立行政法人国立がん研究センター, 東病院, 科長 (40274659)
• Co-Investigator(Kenkyū-buntansha): IMAIZUMI Yoshitaka 長崎大学, 大学病院, 助教 (40404305)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2011: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: HTLV-1 / キャリア / ATL / くすぶり型 / 多段階発がん / 併合解析 / 中間群 / 低悪性度

Research Abstract

To better understand indeterminate HTLV-1 carriers and indolent ATL, ATL-related biomarkers were examined in 57 indolent cases, including unusual carriers with a ATL-like cells. According to Southern blot hybridization analytic features, 28 pts with smoldering ATL could be divided into 3 groups consisting of 16 pts with a monoclonal band, 6 with oligoclonal bands and the remaining 6 with smears. Although no clinical differences were observed among the 3 subtypes, HTLV-1-infected CD4 T-cell counts increased in order of poly-, oligo- and monoclonal subtypes. This trend began in the carrier stage and also was observed in proviral load, CD25 and CCR4, indicating that a clone consisting of leukemic phenotypic cells was continuously growing. Then we evaluated clinical/molecular features in transformation of indolent ATL. Advanced PS, multi-organ involvement and high LDH/Ca values were frequent, and tumor suppressor genes and CD58 alterations were involved in the transformation.

Research Products

• [Journal Article] Meeting report on the possible proposal of an extranodal primary cutaneous variant in the lymphoma type of adult T-cell leukemia-lymphoma (2014)
  • Author(s): Tsukasaki K, Imaizumi Y, Tokura Y, Ohshima K, Kawai K, Utsunomiya A, Amano M,Watanabe T, Nakamura S, Iwatsuki K, Kamihira S, Yamaguchi K, Shimoyama M
  • Journal Title: J Dermatol Volume: 41(1) Pages: 26-8
• [Journal Article] Meeting report on the possible proposal of an extranodal primary cutaneous variant in the lymphoma type of adult T-cell leukemia-lymphoma. (2014)
  • Author(s): Tsukasaki K, Imaizumi Y, Tokura Y, Ohshima K, Kawai K, Utsunomiya A, Amano M,Watanabe T, Nakamura S, Iwatsuki K, Kamihira S, Yamaguchi K, Shimoyama M.
  • Journal Title: The Journal of Dermatology Volume: 41(1) Pages: 26-8
• [Journal Article] Biology and treatment of HTLV-1 associated T-cell lymphomas (2013)
  • Author(s): Tsukasaki K, Tobinai K
  • Journal Title: Best Pract Res Clin Haematol Volume: 26 Pages: 3-14
• [Journal Article] Lymphoma study group of JCOG (2012)
  • Author(s): Tsukasaki K, Tobinai K, Hotta T, Shimoyama M
  • Journal Title: Jpn J Clin Oncol Volume: 42 Pages: 85-95
• [Journal Article] Prognostic index for acute- and lymphoma-type adult T-cell leukemia/lymphoma (2012)
  • Author(s): Katsuya H, Yamanaka T, Ishitsuka K, Utsunomiya A, Sasaki H, Hanada S, Eto T, Moriuchi Y, Saburi Y, Miyahara M, Sueoka E, Uike N, Yoshida S, Yamashita K,Tsukasaki K, Suzushima H, Ohno Y, Matsuoka H, Jo T, Suzumiya J, Tamura K
  • Journal Title: J Clin Oncol Volume: 30 Pages: 1635-40
• [Journal Article] Heterogeneity in clonal nature in the smoldering subtype of adult T-cell leukemia : continuity from carrier status to smoldering ATL (2012)
  • Author(s): Kamihira S, Iwanaga M, Doi Y, Sasaki D, Mori S, Tsurda K, Nagai K, Uno N,Hasegawa H, Yanagihara K, Morinaga Y, Tsukasaki K, Taniguchi H
  • Journal Title: Int J Hematol Volume: 5 Pages: 399-408
  • NAID: 10030632587
• [Journal Article] Defucosylated anti-CCR4 monoclonal antibody (KW-0761) for relapsed adult T-cell leukemia-lymphoma : a multicenter phase II study (2012)
  • Author(s): Ishida T, Joh T, Uike N, Yamamoto K, Utsunomiya A, Yoshida S, Saburi Y,Miyamoto T, Takemoto S, Suzushima H, Tsukasaki K, Nosaka K, Fujiwara H, IshitsukaK, Inagaki H, Ogura M, Akinaga S, Tomonaga M, Tobinai K, Ueda R
  • Journal Title: J Clin Oncol Volume: 30 Pages: 837-42
• [Presentation] Phase I dose-escalation study of Lenalidomide in relapsed patients with ATL or PTCL (2013)
  • Author(s): Imaizumi Y, Ogura M, Uike N, Asou N, Utsunomiya A, Uchida T, Aoki T, Tsukaski K, Taguchi J, Choi I, Maruyama D, Nosaka K, Chen N, Shiota T, Tobinai K
  • Organizer: 第75回日本血液学会学術集会
  • Place of Presentation: 札幌
• [Presentation] Randomized PhaseIIstudy of mLSG15 plus mogamulizumab vs mLSG15 alone for untreated , aggressive ATL (2013)
  • Author(s): Uozumi K, Ishida T, T jo T, Suzushima H, Takemoto S, Yamamoto K, Uike N, Saburi Y, Nosaka K, Utsunomiya A, Tobinai K, fujiwara H, Ishituka K, Yoshida Y, Taira N, Moriuchi U,I mada K, Miyamot T, Tsukasaki K, Tomonaga M, Ueda R
  • Organizer: 第75回日本血液学会学術集会
  • Place of Presentation: 札幌
• [Presentation] Change in NK cell number and activity resulting from first-line chemotherapy for ATL/PTCL (2013)
  • Author(s): Utsunomiya A , Takashi Ishida, Tsukasaki K, akahashi T, Ogura M
  • Organizer: 第75回日本血液学会学術集会
  • Place of Presentation: 札幌
• [Presentation] Re-evolution of VCAP-AMP-VECP in clinical for aggressive adult T-cell leukemia lymphoma (2013)
  • Author(s): Makiyama J, Imaizumi Y, Taniguchi H, Sawayama Y, Imanishi D, Taguchi J, Tsushima H, Hata T, Tsukasaki K, Miyazaki Y
  • Organizer: 第75回日本血液学会学術集会
  • Place of Presentation: 札幌
• [Presentation] NVP-AUY922,a heat shock protein 90 inhibitor, has potent antitumor activity in adult T-cell leukemia lymphoma (2013)
  • Author(s): Taniguchi H, Hasegawa H, Imaizumi Y, Tsukasaki K, Mori N, Miyazaki Y
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: 横浜
• [Presentation] Cell cycle-related gene alterations are involved in transformation of chronic ATL (2013)
  • Author(s): Yoshida N, Karube K, Utsunomiya A, Tsukasaki K, Imaizumi Y, Taira N, Uike N, Umino A, Arita K, Katayama M, Tsuzuki S, Ohsima K, Seto M
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: 横浜
• [Presentation] Combination of Mogamulizumab (KW-0761) with VCAPAMPVECP(MLSG15)is well tolerated and effective as an initial therapy for against Adult T-cell Leukemia Lymphoma(ATL) (2013)
  • Author(s): Takemoto S, Ishida T, Jo T, Uozumi K, Suzushima H, Yamamoto K, Uike N, Saburi Y, Nosaka K, Utusnomiya A, Tobinai K, Fujiara H, Ishitsuka K, Yoshida S, Taira N, Moriuchi Y, Imada K, Miyamoto T, Tsukasaki K, Tomonaga M, Ueda R
  • Organizer: 12th international conference on malignant lymphoma, Lugano
• [Presentation] Cell cycle関連遺伝子の異常は慢性型ATLLの急性転化に関与する (2013)
  • Author(s): 吉田雅明、加留部謙之輔、宇都宮與、塚崎邦弘、今泉芳孝、平良直也、鵜池直邦、海野啓、在田幸太郎、片山幸、都筑忍、大島孝一、瀬戸加大
  • Organizer: 第53回日本リンパ網内系学会
  • Place of Presentation: 京都
• [Presentation] 当科における高齢者成人T細胞白血病・リンパ腫の診療実態と治療成績 (2013)
  • Author(s): 牧山純也、今泉芳孝、谷口広明、森脇裕司、澤山靖、今西大輔、田口潤、對馬秀樹、波多智子、塚崎邦弘、宮崎泰司
  • Organizer: 第53回日本リンパ網内系学会
  • Place of Presentation: 京都
• [Presentation] PhaseIDose–Escalation Study of Lenalidomide in Relapsed Patients with Adult T-cell Leukemia-Lymphoma (ATL) or Peripheral T-cell Lymphoma (PTCL) (2013)
  • Author(s): Maruyama D, Ogura M, Imaizumi Y, Uike N, Asou N, Utsunomiya A, Uchida T ,Aoki T, Tsukasaki K, Taguchi J, Choi I , Shiota T, Nosaka K, Chen N, Tobinai K
  • Organizer: 5th Annual T-cell Lymphoma Forum
  • Place of Presentation: San Francisco
• [Presentation] Cell cycle-related gene alterations are involved in transformation of chronic ATL. (2013)
  • Author(s): Yoshida N, Karube K, Utsunomiya A, Tsukasaki K, Imaizumi Y, Taira N, Uike N, Umino A, Arita K, Katayama M, Tsuzuki S, Ohsima K, Seto M
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜（横浜市）
• [Presentation] Multicenter Phase I Dose-Escalation Study of Lenalidomide in Patients with Relapsed Adult T-Cell Leukemia-Lymphoma (ATL) or Peripheral T-Cell Lymphoma (PTCL) (2012)
  • Author(s): Uike N, Ogura M, Imaizumi Y, Asou N, Utsunomiya A, Uchida T, Aoki T, Tsukasaki K, Taguchi J, Choi I, Maruyama D, Nosaka K, Chen N, Shiota T, Tobinai K
  • Organizer: 54th ASH Annual Meeting
  • Place of Presentation: Atlanta
• [Presentation] CD26 antigen acts as a predictive biomarker in the evolution of ATL : continuity from carrier status to smoldering ATL (2012)
  • Author(s): Hasegawa H, Tsukasaki K, Miyazaki Y, Kamihira S
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 札幌
• [Presentation] CD26 antigen act as a predictive biomarker in the evolution from early to overt smoldering ATL (2012)
  • Author(s): Hasegawa H, Tsukasaki K, Tsuruda K , Sasaki D, Doi Y, Mori S, Ishihara K, Nagai K, Yanagihara K, Miyazaki Y, Kamihira H
  • Organizer: 第74回日本血液学会学術集会
  • Place of Presentation: 京都
• [Presentation] Lymphoma cases without detectable monoclonal HTLV-1 integration in HTLV-1 carrier (2012)
  • Author(s): Imaizumi Y, Tsukasaki K, Tsushima H, Matsuo M, Sasaki D, Hasegawa H, Kamihira S, Niini D, Ohshima K, Miyazaki Y
  • Organizer: 第74回日本血液学会学術集会
  • Place of Presentation: 京都
• [Presentation] Impact of miR-155 and miR-126 as novel biomarkers on the assessment of disease progression in ATL (2012)
  • Author(s): Ishihara K, Tsukasaki K, Hasegawa H, Sasaki D, Tsuruda K, Inokouchi N, Nagai K, Yanagihara K, Miyazaki Y Kamihira S
  • Organizer: 第74回日本血液学会学術集会
  • Place of Presentation: 京都
• [Presentation] Lymphoma cases without detectable monoclonal HTLV-1 integration in HTLV-1 carrier. (2012)
  • Author(s): Imaizumi Y, Tsukasaki K, et al:
  • Organizer: 第74回日本血液学会学術集会,2012.
  • Place of Presentation: 京都
• [Book] [Rare Lymphomas] 8.Adult T-cell Leukemia Lymphoma. Edior : Martin Dreying, Maicheal E. Williams (2014)
  • Author(s): Tsukasaki K, Tobinai K
  • Publisher: Springer-Verlag Berlin Heidelberg
• [Book] [T-cell Lymphomas] 8.HTLV-1-Assorted T-cell Diseases. Edior : Francine Foss (2013)
  • Author(s): Tsukasaki K, Tobinai K
  • Publisher: Springer Science/Business Media New York