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OIIA-LPD and genetic alteration

Research Project

Project/Area Number 18K16076
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 54010:Hematology and medical oncology-related
Research InstitutionUniversity of Tsukuba

Principal Investigator

Kusakabe Manabu  筑波大学, 医学医療系, 講師 (40804381)

Project Period (FY) 2018-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2019: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords悪性リンパ腫 / 医原性リンパ増殖性疾患 / 次世代シーケンス / 遺伝子変異 / 自己免疫疾患 / メソトレキセート / シーケンス / 予後予測
Outline of Final Research Achievements

We identified 64 cases of OIIA-LPD. Histological type in lymph node biopsy, autoimmune disease that triggered the initiation of oral administration of immunosuppressant, presence or absence of immunosuppressant, response after immunosuppressant discontinuation, presence or absence of chemotherapy, response to chemotherapy, and clinical information were extracted and analyzed. Similar to the previous report, about half of the histological types were DLBCL and about 1/3 were Hodgkin lymphoma. We were able to extract decent amount of genomic DNA from all of fresh frozen specimens and about half of the FFPE specimens for sequence analysis. A sequence library targeting the 412 gene associated with lymphoid tumor was prepared and sequenced with HiSeq 4000. In the future, we plan to analyze using sequence results and clinical information.

Academic Significance and Societal Importance of the Research Achievements

自己免疫疾患に罹患した患者の治療薬としてメソトレキセートなどの免疫抑制剤は広く用いられている。そのような免疫抑制剤を内服している患者の一部にリンパ増殖性疾患という悪性リンパ腫に類似した病態を示すことがある。本研究はそのようなリンパ増殖性疾患(OIIA-LPD)を対象として、その組織型や免疫抑制剤中止への反応、抗がん剤を用いた化学療法の必要性などの情報を収集した。また診断の根拠となった臨床検体を材料として遺伝子変異を解析した。これらの結果を統合することでOIIA-LPDの臨床像や病態を明らかにすることを目的とした。

Report

(3 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • Research Products

    (18 results)

All 2020 2019 2018

All Journal Article (16 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 16 results,  Open Access: 10 results) Presentation (2 results) (of which Int'l Joint Research: 2 results)

  • [Journal Article] Molecular pathogenesis of progression to myeloid leukemia from TET-insufficient status.2020

    • Author(s)
      Shrestha R, Sakata-Yanagimoto M, Maie K, Oshima M, Ishihara M, Suehara Y, Fukumoto K,1 Nakajima-Takagi Y, Matsui H, Kato T, Muto H, Sakamoto T, Kusakabe M, Nannya Y, Makishima H, Ueno H, Saiki R, Ogawa S, Chiba K, Shiraishi Y, Miyano S, Mouly E, Bernard OA, Inaba T, Koseki H, Iwama A, Chiba S
    • Journal Title

      Blood Adv.

      Volume: 4(5) Issue: 5 Pages: 845-854

    • DOI

      10.1182/bloodadvances.2019001324

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Dasatinib is an effective treatment for angioimmunoblastic T-cell lymphoma.2020

    • Author(s)
      Nguyen TB, Sakata-Yanagimoto M, Fujisawa M, Tanzima Nuhat S, Miyoshi H, Nannya Y, Hashimoto K, Fukumoto K, Bernard OA, Kiyoki Y, Ishitsuka K, Momose H, Sukegawa S, Shinagawa A, Suyama T, Sato Y, Nishikii H, Obara N, Kusakabe M, Yanagimoto S, Ogawa S, Ohshima K, Chiba S.
    • Journal Title

      Cancer Res. 2020.

      Volume: - Issue: 9 Pages: 1875-1884

    • DOI

      10.1158/0008-5472.can-19-2787

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Occurrence of T-cell and NK-cell subsets with less well-recognized phenotypes in peripheral blood submitted for routine flow cytometry analysis2020

    • Author(s)
      Hill Ainsleigh J.、Zhang Chaoran、Kusakabe Manabu、Gowing Kevin、Wang Xuehai、Brinkman Ryan R.、Weng Andrew P.、Craig Jeffrey W.
    • Journal Title

      Cytometry Part B: Clinical Cytometry

      Volume: - Issue: 2 Pages: 1-5

    • DOI

      10.1002/cyto.b.21876

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Single Cell Phenotypic Profiling of 27 DLBCL Cases Reveals Marked Intertumoral and Intratumoral Heterogeneity2019

    • Author(s)
      Nissen MD、Kusakabe M、Wang X、Simkin G、Gracias D、Tyshchenko K、Hill A、Meskas J、Hung S、Chavez EA、Ennishi D、Aoki T、Sarkozy C、Connors JM、Farinha P、Slack GW、Gascoyne RD、Brinkman RR、Scott DW、Steidl C、Weng AP
    • Journal Title

      Cytometry Part A

      Volume: - Issue: 6 Pages: 1-10

    • DOI

      10.1002/cyto.a.23919

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Synthetic modeling reveals HOXB genes are critical for the initiation and maintenance of human leukemia2019

    • Author(s)
      Kusakabe M、Sun AC、Tyshchenko K、Wong R、Nanda A、Shanna C、Gusscott S、Chavez EA.、Lorzadeh A、Zhu A、Hill A、Hung S、Brown S、Babaian A、Wang X、Holt RA、Steidl C、Karsan A、Humphries RK、Eaves CJ、Hirst M、Weng AP
    • Journal Title

      Nature Communications

      Volume: 10 Issue: 1 Pages: 1-15

    • DOI

      10.1038/s41467-019-10510-8

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Mutations found in cell-free DNAs of patients with malignant lymphoma at remission can derive from clonal hematopoiesis2019

    • Author(s)
      Suehara Y, Sakata-Yanagimoto M, Hattori K, Kusakabe M, Nanmoku T, Sato T, Noguchi M, Chiba S
    • Journal Title

      Cancer Sci

      Volume: 110(10) Issue: 10 Pages: 3375-3381

    • DOI

      10.1111/cas.14176

    • NAID

      120007133006

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The prognosis of disseminated intravascular coagulation associated with hematologic malignancy and its response to recombinant human thrombomodulin2019

    • Author(s)
      Kurita Naoki、Sakamoto Tatsuhiro、Kato Takayasu、Kusakabe Manabu、Yokoyama Yasuhisa、Nishikii Hidekazu、Sakata-Yanagimoto Mamiko、Obara Naoshi、Hasegawa Yuichi、Chiba Shigeru
    • Journal Title

      Thrombosis Research

      Volume: 173 Pages: 57-64

    • DOI

      10.1016/j.thromres.2018.11.014

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Durable Leukemic Remission and Autologous Marrow Recovery with Random Chromosomal Abnormalities after Allogeneic Hematopoietic Stem Cell Transplantation for Chronic Lymphocytic Leukemia2019

    • Author(s)
      Nishikii Hidekazu、Kurita Naoki、Shinagawa Atsushi、Sakamoto Tatsuhiro、Kusakabe Manabu、Yokoyama Yasuhisa、Kato Takayasu、Sakata-Yanagimoto Mamiko、Obara Naoshi、Hasegawa Yuichi、Nakamura Naoya、Chiba Shigeru
    • Journal Title

      Case Reports in Hematology

      Volume: 2019 Pages: 1-5

    • DOI

      10.1155/2019/9710790

    • NAID

      120007128070

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Successful management of primary immune thrombocytopenia with romiplostim during open heart surgery in a hemodialysis patient2019

    • Author(s)
      錦井 秀和、栗田 尚樹、日下部 学、横山 泰久、加藤 貴康、坂田(柳元) 麻実子、小原 直、長谷川 雄一、千葉 滋
    • Journal Title

      Rinsho Ketsueki

      Volume: 60 Issue: 1 Pages: 28-32

    • DOI

      10.11406/rinketsu.60.28

    • NAID

      130007590727

    • ISSN
      0485-1439, 1882-0824
    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] An Unprecedented Case of p190 BCR-ABL Chronic Myeloid Leukemia Diagnosed during Treatment for Multiple Myeloma: A Case Report and Review of the Literature2018

    • Author(s)
      Miki Kosuke、Obara Naoshi、Makishima Kenichi、Sakamoto Tatsuhiro、Kusakabe Manabu、Kato Takayasu、Kurita Naoki、Nishikii Hidekazu、Yokoyama Yasuhisa、Sakata-Yanagimoto Mamiko、Hasegawa Yuichi、Chiba Shigeru
    • Journal Title

      Case Reports in Hematology

      Volume: 2018 Pages: 1-5

    • DOI

      10.1155/2018/7863943

    • NAID

      120007128268

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] High efficacy of eculizumab treatment for fulminant hemolytic anemia in primary cold agglutinin disease2018

    • Author(s)
      Makishima Kenichi、Obara Naoshi、Ishitsuka Kantaro、Sukegawa Shinichiro、Suma Sakurako、Kiyoki Yusuke、Baba Naoko、Sakamoto Tatsuhiro、Kato Takayasu、Kusakabe Manabu、Nishikii Hidekazu、Kurita Naoki、Yokoyama Yasuhisa、Sakata-Yanagimoto Mamiko、Hasegawa Yuichi、Chiba Shigeru
    • Journal Title

      Annals of Hematology

      Volume: 98 Issue: 4 Pages: 1031-1032

    • DOI

      10.1007/s00277-018-3521-4

    • NAID

      120007128039

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Genetic evidence implies that primary and relapsed tumors arise from common precursor cells in primary central nervous system lymphoma2018

    • Author(s)
      Hattori Keiichiro、Sakata-Yanagimoto Mamiko、Kusakabe Manabu、Nanmoku Toru、Suehara Yasuhito、Matsuoka Ryota、Noguchi Masayuki、Yokoyama Yasuhisa、Kato Takayasu、Kurita Naoki、Nishikii Hidekazu、Obara Naoshi、Takano Shingo、Ishikawa Eiichi、Matsumura Akira、Muratani Masafumi、Hasegawa Yuichi、Chiba Shigeru
    • Journal Title

      Cancer Science

      Volume: 110 Issue: 1 Pages: 401-407

    • DOI

      10.1111/cas.13848

    • NAID

      120007128280

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Blastic plasmacytoid dendritic cell neoplasm arising from clonal hematopoiesis2018

    • Author(s)
      Suma Sakurako、Sakata-Yanagimoto Mamiko、Nguyen Tran B.、Hattori Keiichiro、Sato Taiki、Noguchi Masayuki、Nannya Yasuhito、Ogawa Seishi、Watanabe Rei、Fujimoto Manabu、Nakamura Naoya、Kusakabe Manabu、Nishikii Hidekazu、Kato Takayasu、Chiba Shigeru
    • Journal Title

      International Journal of Hematology

      Volume: 108 Issue: 4 Pages: 447-451

    • DOI

      10.1007/s12185-018-2461-z

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Liquid biopsy for the identification of intravascular large B-cell lymphoma2018

    • Author(s)
      Suehara Yasuhito、Sakata-Yanagimoto Mamiko、et al
    • Journal Title

      Hematologica

      Volume: in press Issue: 6 Pages: e241-e244

    • DOI

      10.3324/haematol.2017.178830

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Droplet digital PCR assay and PNA-LNA clamp method for RHOA mutation detection in angioimmunoblastic T-cell lymphoma2018

    • Author(s)
      Tanzima Nuhat S, Sakata-Yanagimoto M, Komori D, Hattori K, Suehara Y, Fukumoto K, Fujisawa M, Kusakabe M, Matsue K, Wakamatsu H, Shimadzu M, Chiba S
    • Journal Title

      Cancer Sci

      Volume: - Issue: 5 Pages: 1682-1689

    • DOI

      10.1111/cas.13557

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Blastic plasmacytoid dendritic cell neoplasm accompanied by chronic myelomonocytic leukemia successfully treated with azacitidine2018

    • Author(s)
      助川 慎一郎、横山 泰久、錦井 秀和、加藤 貴康、日下部 学、栗田 尚樹、小原 直、長谷川 雄一、千葉 滋、坂田(柳元) 麻実子、松岡 亮太、百瀬 春佳、清木 祐介、野口 雅之、中村 直哉、渡辺 玲、藤本 学
    • Journal Title

      Rinsho Ketsueki

      Volume: 59 Issue: 12 Pages: 2567-2573

    • DOI

      10.11406/rinketsu.59.2567

    • NAID

      130007554669

    • ISSN
      0485-1439, 1882-0824
    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Presentation] Targeted sequencing and IgH rearrangement status revealed branching evolution pattern of SMZL and DLBCL2019

    • Author(s)
      Manabu Kusakabe
    • Organizer
      The 10th JSH INTERNATIONAL SYMPOSIUM 2019 in Ise-Shima
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Clinicopathological Analysis of “Other Iatrogenic Immunodeficiency-Associated Lymphoproliferative Disorders” Reveals a Favorable Outcome Independent of the Effectiveness of Methotrexate Discontinuation in Autoimmune Disease Patients2019

    • Author(s)
      Daisuke Kaji
    • Organizer
      61st ASH Annual Meeting and Exposition
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research

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Published: 2018-04-23   Modified: 2021-02-19  

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