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The Association of STAT3 Activation with Interferon Therapy in Adult T-Cell Leukemia Lymphoma

Research Project

Project/Area Number 19K17862
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 the Ryukyus

Principal Investigator

MORICHIKA KAZUHO  琉球大学, 医学(系)研究科(研究院), 助教 (90793943)

Project Period (FY) 2019-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2021: ¥260,000 (Direct Cost: ¥200,000、Indirect Cost: ¥60,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywordsadult T cell lymphoma / STAT3 / immunohistochemistry / DNA sequencing / DLBCL / リン酸化 / DNAシークエンシング / びまん性大細胞型B細胞リンパ腫 / GCB型 / non-GCB型 / シークエンス / 免疫染色 / 成人T細胞性白血病 / 免疫組織化学染色 / 遺伝子変異 / JAK-STAT3経路 / 予後予測マーカー / HTLV-1 / JAK-STAT経路 / 内科 / 成人T細胞性白血病リンパ腫 / インターフェロン療法
Outline of Research at the Start

本研究では九州・沖縄地方において発症頻度が高い成人T細胞性白血病(Adult T-cell leukemia/lymphoma, ATLL)におけるSTAT3タンパクとIFN-αの腫瘍増殖抑制効果との関連性の詳細な解明を目指す。この研究によって、IFN-α/zudovudine療法の治療標的が同定され、治療適応基準と予後改善への貢献を目指す。

Outline of Final Research Achievements

Adult T-cell leukemia/lymphoma (ATLL) is a mature T-cell neoplasm, and is divided into 2 indolent (smoldering and chronic) and 2 aggressive (acute and lymphoma) clinical subtypes. We attempted to clarify the clinicopathological significance of JAK-STAT pathway. Clinical and morphological findings were reviewed in 116 cases with ATLL. The nuclear localizations of phosphorylated STAT3, 5, 6 (pSTAT) were analyzed by immunohistochemistry. Targeted sequencing was undertaken on the portion of STAT3 encoding the Src homology 2 domain. Both univariate and multivariate analysis revealed that pSTAT3 expression was significantly associated with better overall survival and progression-free survival in the smoldering type of ATLL, whereas STAT3 mutation was not related to a line of clinical outcome. Collectively, our data raises the possibility that pSTAT3 expression is a novel biomarker to predict better prognosis in the smoldering type of ATLL.

Academic Significance and Societal Importance of the Research Achievements

上記に示す様にくすぶり型ATLにおける新たな予後因子を提唱した。さらに我々はびまん性大細胞型B細胞リンパ腫におけるpSTAT3の意義についても解析した。pSTAT3陽性GCB型は5年生存率が92%であるのに対し、pSTAT3陽性non-GCB型は45%と、Cell of OriginによりpSTAT3発現の臨床的意義が異なっていた。pSTAT3陽性GCB型は多変量解析でも予後良好因子として抽出された。遺伝子変異解析の結果、MYD88変異、EZH2変異、EBウイルス感染、BCL2/MYCの再構成といった予後不良とされる分子異常を伴う頻度が有意に低いことが予後良好と関連する背景として考えられた。

Report

(5 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (11 results)

All 2023 2022 2021 2020 2019

All Journal Article (6 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 6 results,  Open Access: 6 results) Presentation (5 results)

  • [Journal Article] Clinically amyopathic dermatomyositis manifested after the allogeneic haematopoietic stem cell transplantation: Case presentation and literature review2023

    • Author(s)
      Miyagi R, Nakachi S, Tamaki Y, Doi M, Nakajima T, Kitamura S, Tomori S, Hanashiro T, Tamaki K, Morichika K, Nishi Y, Morishima S, Fukushima T, Masuzaki H.
    • Journal Title

      Mod Rheumatol Case Rep

      Volume: 7 Pages: 102-107

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The Positivity of Phosphorylated STAT3 Is a Novel Marker for Favorable Prognosis in Germinal Center B-Cell Type of Diffuse Large B-Cell Lymphoma2021

    • Author(s)
      K. Morichika, K. Karube, S. Sakihama, R. Watanabe, M. Kawaki, Y. Nishi, S. Nakachi, S. Okamoto, T. Takahara, A. Satou, S. Shimada, K. Shimada, T. Tsuzuki, T. Fukushima, S. Morishima and H. Masuzaki
    • Journal Title

      Am J Surg Pathol

      Volume: - Issue: 6 Pages: 832-840

    • DOI

      10.1097/pas.0000000000001691

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Genetic profile of adult T‐cell leukemia/lymphoma in Okinawa: Association with prognosis, ethnicity, and HTLV‐1 strains2021

    • Author(s)
      Sakihama Shugo、Morichika Kazuho、Saito Rumiko、Miyara Megumi、Miyagi Takashi、Hayashi Masaki、Uchihara Junnosuke、Tomoyose Takeaki、Ohshiro Kazuiku、Nakayama Shingo、Nakachi Sawako、Morishima Satoko、Sakai Kazuko、Nishio Kazuto、Masuzaki Hiroaki、Fukushima Takuya、Karube Kennosuke
    • Journal Title

      Cancer Science

      Volume: 112 Issue: 3 Pages: 1300-1309

    • DOI

      10.1111/cas.14806

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Clinicopathological features of adult T-cell leukemia/lymphoma with HTLV-1-infected Hodgkin and Reed-Sternberg-like cells2021

    • Author(s)
      Kennosuke Karube, Mitsuyoshi Takatori, Shugo Sakihama, Yuma Tsuruta, Takashi Miyagi, Kazuho Morichika, Sakiko Kitamura, Norihiro Nakada, Masaki Hayashi, Shohei Tomori, Iwao Nakazato, Kazuiku Ohshiro, Naoki Imaizumi, Yara Yukie Kikuti, Naoya Nakamura, Satoko Morishima, Hiroaki Masuzaki, Takuya Fukushima
    • Journal Title

      Blood Advances

      Volume: 5 Pages: 198-206

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Full-length HLA sequencing in adult T cell leukemia-lymphoma uncovers multiple gene alterations.2021

    • Author(s)
      Tamaki K, Morishima S, Suzuki S, Shigenari A, Nomura I, Yokota Y, Morichika K, Nishi Y, Nakachi S, Okamoto S, Fukushima T, Shiina T, Masuzaki H.
    • Journal Title

      Leukemia

      Volume: 35 Issue: 10 Pages: 2998-3001

    • DOI

      10.1038/s41375-021-01403-1

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Phosphorylated STAT3 expression predicts better prognosis in smoldering type of adult T-cell leukemia/lymphoma.2019

    • Author(s)
      Morichika K, Karube K, Kayo H, Uchino S, Nishi Y, Nakachi S, Okamoto S, Morishima S, Ohshiro K, Nakazato I, Fukushima T, Masuzaki H.
    • Journal Title

      Cancer Sci.

      Volume: 110 Issue: 9 Pages: 2982-2991

    • DOI

      10.1111/cas.14114

    • NAID

      120006937802

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 眼房水のIL-10/IL-6濃度比が診断と病勢評価に有用であった原発性網膜硝子体リンパ腫2022

    • Author(s)
      森近一穂
    • Organizer
      第336回 日本内科学会九州地方会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Indolent ATLにおける診断時血清sIL-2R値の2倍化は優れた急性転化予測指標である2021

    • Author(s)
      森近一穂、森島聡子、北村紗希子、友利昌平、玉城啓太、西由希子、仲地佐和子、宮城敬、大城一郁、福島卓也、加留部謙之輔、益崎裕章
    • Organizer
      第7回HTLV-1学会
    • Related Report
      2021 Research-status Report
  • [Presentation] 遺伝子全領域の解析により明らかになったATLに生じる多彩なHLA遺伝子異常2021

    • Author(s)
      森島聡子、玉城啓太、鈴木進悟、重成敦子、野村育美、横田雄太郎、森近一穂、西由希子、仲地佐和子、岡本士毅、福島卓也、椎名隆、益崎裕章
    • Organizer
      第7回HTLV-1学会
    • Related Report
      2021 Research-status Report
  • [Presentation] 血清sIL-2R濃度の持続的上昇はインドレント型ATL における急性転化の予測に有用である2020

    • Author(s)
      森近一穂
    • Organizer
      日本内科学会九州地方会
    • Related Report
      2020 Research-status Report
  • [Presentation] 血清sIL-2R濃度の持続的上昇はインドレント型ATL における急性転化の予測に有用である2020

    • Author(s)
      森近一穂
    • Organizer
      日本血液学会九州地方会
    • Related Report
      2020 Research-status Report

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Published: 2019-04-18   Modified: 2024-01-30  

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