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Elucidation of molecular epidemiology and pathophysiology of acquired sideroblastic anemia

Research Project

Project/Area Number 18K08314
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 54010:Hematology and medical oncology-related
Research InstitutionTohoku University

Principal Investigator

Fujiwara Tohru  東北大学, 大学病院, 講師 (60333796)

Project Period (FY) 2018-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords後天性鉄芽球性貧血 / 鉄芽球性貧血 / 骨髄異形成症候群
Outline of Final Research Achievements

Acquired sideroblastic anemia, characterized by bone marrow ring sideroblasts (RS), is predominantly associated with myelodysplastic syndrome (MDS). Although somatic mutations in splicing factor 3b subunit 1 (SF3B1), which is involved in the RNA splicing machinery, are frequently found in MDS-RS, the detailed mechanism contributing to RS formation is unknown. To explore the mechanism, we established human umbilical cord blood-derived erythroid progenitor-2 (HUDEP-2) cells stably expressing SF3B1K700E. SF3B1K700E expressing cells showed higher proportion of RS than the control cells along with erythroid differentiation. In SF3B1K700E expressing cells, ABCB7 and ALAS2, known causative genes for congenital sideroblastic anemia, were downregulated. ABCB7-knockdown HUDEP-2 cells revealed an increased frequency of RS formation along with erythroid differentiation. Finally, RNA-seq analysis of MDS clinical samples demonstrated decreased expression of ABCB7 by the SF3B1 mutation.

Academic Significance and Societal Importance of the Research Achievements

後天性鉄芽球性貧血の代表であるMDS-RSにおける環状鉄芽球形成機序について、先天性と共通の分子基盤が存在する可能性があるが、この点について包括的な解析を行った報告は国内外を含め認められない。本分子基盤の一端を明らかにしたことは、MDS-RSのみならず鉄芽球性貧血全体の病態の理解に繋がるだけでなく、MDS-RSへの新規治療法の開発にも繋がる可能性がある。また、本研究成果が赤芽球におけるヘム・鉄代謝に関する未知の生理的機構の解明に繋がる可能性もある。

Report

(5 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (35 results)

All 2022 2021 2020 2019 2018

All Journal Article (16 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 16 results,  Open Access: 7 results) Presentation (19 results) (of which Int'l Joint Research: 10 results,  Invited: 2 results)

  • [Journal Article] Unrelated cord blood transplantation for adult-onset EBV-associated T-cell and NK-cell lymphoproliferative disorders2022

    • Author(s)
      Onishi Yasushi、Onodera Koichi、Fukuhara Noriko、Kato Hiroki、Ichikawa Satoshi、Fujiwara Tohru、Yokoyama Hisayuki、Yamada-Fujiwara Minami、Harigae Hideo
    • Journal Title

      International Journal of Hematology

      Volume: - Issue: 6 Pages: 873-881

    • DOI

      10.1007/s12185-022-03313-z

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Salvage Cord Blood Transplantation for Sustained Remission of Acute Megakaryoblastic Leukemia That Relapsed Early after Myeloablative Transplantation2021

    • Author(s)
      Ichikawa Satoshi、Fujiwara Tohru、Saito Kei、Sakurai Kazuki、Inokura Kyoko、Fukuhara Noriko、Yokoyama Hisayuki、Onodera Koichi、Onishi Yasushi、Kameoka Junichi、Harigae Hideo
    • Journal Title

      Internal Medicine

      Volume: 60 Issue: 18 Pages: 3015-3019

    • DOI

      10.2169/internalmedicine.6796-20

    • NAID

      130008088286

    • ISSN
      0918-2918, 1349-7235
    • Year and Date
      2021-09-15
    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Targeting stanniocalcin‐1‐expressing tumor cells elicits efficient antitumor effects in a mouse model of human lung cancer2021

    • Author(s)
      Abe Kotaro、Kanehira Masahiko、Ohkouchi Shinya、Kumata Sakiko、Suzuki Yamato、Oishi Hisashi、Noda Masafumi、Sakurada Akira、Miyauchi Eisaku、Fujiwara Tohru、Harigae Hideo、Okada Yoshinori
    • Journal Title

      Cancer Medicine

      Volume: 10 Issue: 9 Pages: 3085-3100

    • DOI

      10.1002/cam4.3852

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Acquisition of monosomy 7 and a RUNX1 mutation in Pearson syndrome2020

    • Author(s)
      Nishimura Akira、Hirabayashi Shinsuke、Hasegawa Daisuke、Yoshida Kenichi、Shiraishi Yuichi、Ashiarai Miho、Hosoya Yosuke、Fujiwara Tohru、Harigae Hideo、Miyano Satoru、Ogawa Seishi、Manabe Atsushi
    • Journal Title

      Pediatric Blood & Cancer

      Volume: 68 Issue: 2

    • DOI

      10.1002/pbc.28799

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A novel case of γδ T cell leukemia with recurrent genetic abnormalities accompanied by agranulocytosis2020

    • Author(s)
      Ichikawa Satoshi、Fujiwara Tohru、Saito Kei、Fukuhara Noriko、Yokoyama Hisayuki、Hatta Shunsuke、Onodera Koichi、Onishi Yasushi、Fujishima Fumiyoshi、Ichinohasama Ryo、Harigae Hideo
    • Journal Title

      Annals of Hematology

      Volume: - Issue: 10 Pages: 2665-2668

    • DOI

      10.1007/s00277-020-04241-w

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] 環状鉄芽球と鉄代謝2020

    • Author(s)
      藤原 亨
    • Journal Title

      臨床血液

      Volume: 61 Pages: 770-778

    • NAID

      130007884764

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Flow Cytometry-Based Photodynamic Diagnosis with 5-Aminolevulinic Acid for the Detection of Minimal Residual Disease in Multiple Myeloma2019

    • Author(s)
      Iwaki K, Fujiwara T, Ito T, Suzuki C, Sasaki K, Ono K, Saito K, Fukuhara N, Onishi Y, Yokoyama H, Fujimaki S, Tanaka T, Tamura H, Fujiwara M, Harigae H
    • Journal Title

      The Tohoku Journal of Experimental Medicine

      Volume: 249 Issue: 1 Pages: 19-28

    • DOI

      10.1620/tjem.249.19

    • NAID

      130007706214

    • ISSN
      0040-8727, 1349-3329
    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Study of pathophysiology and molecular characterization of congenital anemia in India using targeted next-generation sequencing approach2019

    • Author(s)
      Kedar PS, Harigae H, Ito E, Muramatsu H, Kojima S, Okuno Y, Fujiwara T, Dongerdiye R, Warang PP, Madkaikar MR
    • Journal Title

      Int J Hematol

      Volume: 60 Issue: 5 Pages: 408-416

    • DOI

      10.1007/s12185-019-02716-9

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Preemptive therapy for cytomegalovirus reactivation after daratumumab-containing treatment in patients with relapsed and refractory multiple myeloma.2019

    • Author(s)
      Nakagawa R, Onishi Y, Kawajiri A, Onodera K, Furukawa E, Sano S, Saito K, Ichikawa S, Fujiwara T, Fukuhara N, Harigae H.
    • Journal Title

      Ann Hematol.

      Volume: - Issue: 8 Pages: 1999-2001

    • DOI

      10.1007/s00277-019-03645-7

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Sideroblastic anemia2019

    • Author(s)
      Fujiwara T
    • Journal Title

      Rinsho Ketsueki

      Volume: 60 Issue: 5 Pages: 408-416

    • DOI

      10.11406/rinketsu.60.408

    • NAID

      130007659586

    • ISSN
      0485-1439, 1882-0824
    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Generation and Molecular Characterization of Human Ring Sideroblasts: a Key Role of Ferrous Iron in Terminal Erythroid Differentiation and Ring Sideroblast Formation.2019

    • Author(s)
      Saito K, Fujiwara T, Hatta S, Morita M, Ono K, Suzuki C, Fukuhara N, Onishi Y, Nakamura Y, Kawamata S, Shimizu R, Yamamoto M, Harigae H.
    • Journal Title

      Mol Cell Biol.

      Volume: 39 Issue: 7

    • DOI

      10.1128/mcb.00387-18

    • Related Report
      2019 Research-status Report 2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Molecular pathophysiology and genetic mutations in congenital sideroblastic anemia2019

    • Author(s)
      Fujiwara T, Harigae H
    • Journal Title

      Free Radic Biol Med

      Volume: 133 Pages: 179-185

    • DOI

      10.1016/j.freeradbiomed.2018.08.008

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Molecular pathophysiology of sideroblastic anemia2018

    • Author(s)
      Fujiwara T
    • Journal Title

      Rinsho Ketsueki

      Volume: 59 Issue: 10 Pages: 1979-1987

    • DOI

      10.11406/rinketsu.59.1979

    • NAID

      130007496828

    • ISSN
      0485-1439, 1882-0824
    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Infection perturbs Bach2- and Bach1-dependent erythroid lineage chioce to cause anemia2018

    • Author(s)
      Kato H, Itoh-Nakadai A, Matsumoto M, Ishii Y, Watanabe-Matsui M, Ikeda M, Ebina-Shibuya R, Sato Y, Kobayashi M, Nishizawa H, Suzuki K, Muto A, Fujiwara T, Nannya Y, Cazzola M, Ogawa S, Harigae H, Igarashi K
    • Journal Title

      Nat Immunol

      Volume: 19 Issue: 10 Pages: 496-497

    • DOI

      10.1038/s41590-018-0202-3

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Five-aminolevulinic acid: New Approach for Congenital Sideroblastic Anemia2018

    • Author(s)
      Ishida H, Imamura T, Morimoto A, Fujiwara T, Harigae H
    • Journal Title

      Pediatr Int

      Volume: 60 Issue: 5 Pages: 496-497

    • DOI

      10.1111/ped.13558

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] A defined culture method enabling the establishment of ring sideroblasts from induced pluripotent cells of X-linked sideroblastic anemia.2018

    • Author(s)
      1.Hatta S, Fujiwara T, Yamamoto T, Saito K, Kamata M, Tamai Y, Kawamata S, Harigae H.
    • Journal Title

      Haematologica.

      Volume: - Issue: 5 Pages: 188-191

    • DOI

      10.3324/haematol.2017.179770

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] FOG1-dependent transcriptional network involves glucose metabolic regulation of erythroid cells.2021

    • Author(s)
      Fujiwara T, Suzuki C, Ono K, Saito K, Kato H, Onodera K, Ichikawa S, Fukuhara N, Onishi Y, Yokoyama H, Harigae H.
    • Organizer
      第83回日本血液学会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Cellular models of X-linked sideroblastic anemia based on immortalized human erythroid progenitors.2021

    • Author(s)
      Ono K, Fujiwara T, Saito K, Suzuki C, Takahashi N, Kato H, Onodera K, Ichikawa S, Fukuhara N, Onishi Y, Yokoyama H, Nakamura Y, Harigae H.
    • Organizer
      第83回日本血液学会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Monitoring CAR-T cells using flow cytometry: A feasibility study.2021

    • Author(s)
      Fujiwara T, Onishi Y, Niizuma H, Okubo N, Sugawara S, Moriya K, Ichikawa S, Irie M, Fukuhara N, Yokoyama H, Fujiwara M, Fujimaki S, Sasahara Y, Harigae H.
    • Organizer
      第12回日本血液学会国際シンポジウム
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Inhibition of S-Adenosylmethionine synthesis promotes erythropoiesis via epigenetic modifications.2021

    • Author(s)
      Kato H, Long NC, Ishii Y, Matsumoto M, Rhee C, Saigusa D, Funayama R, Okae H, Fujiwara T, Muto A, Harigae H, Scadden DT, Igarashi K.
    • Organizer
      第63回米奥血液学会
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] FOG1-DEPENDENT TRANSCRIPTIONAL NETWORK INVOLVES GLUCOSE METABOLIC REGULATION OF ERYTHROID CELLS.2020

    • Author(s)
      Fujiwara T, Suzuki C, Sasaki K, Sano S, Ono K, Saito K, Onodera K, Ichikawa S, Fukuhara N, Onishi Y, Hisayuki Y, Harigae H.
    • Organizer
      第25回欧州血液学会
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] TRANSCRIPTIONAL REGULATION OF FERROPTOSIS IN X-LINKED SIDEROBLASTIC ANEMIA.2020

    • Author(s)
      Ono K, Fujiwara T, Saito K, Suzuki C, Takahashi N, Yan Y, Onodera K, Ichikawa S, Fukuhara N, Onishi Y, Hisayuki Y, Fujimaki S, Nakamura Y, Harigae H.
    • Organizer
      第62回米国血液学会
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] ROLE OF FERROPTOSIS IN X-LINKED SIDEROBLASTIC ANEMIA.2020

    • Author(s)
      Ono K, Fujiwara T, Saito K, Suzuki C, Takahashi N, Yan Y, Onodera K, Ichikawa S, Fukuhara N, Onishi Y, Hisayuki Y, Fujimaki S, Nakamura Y, Harigae H.
    • Organizer
      第25回欧州血液学会
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] Establishment of congenital sideroblastic anemia model due to ABCB7 defect.2020

    • Author(s)
      Fujiwara T, Ochi T, Suzuki C, Ono K, Saito K, Fukuhara N, Onishi Y, Yokoyama H, Nakamura Y, Harigae H.
    • Organizer
      第82回日本血液学会総会
    • Related Report
      2020 Research-status Report
  • [Presentation] Impact of ferroptosis in X-linked sideroblastic anemia.2020

    • Author(s)
      Ono K, Fujiwara T, Saito K, Suzuki C, Takahshi N, Yan Y, Onodera K, Ichikawa S, Fukuhara N, Onishi Y, Yokoyama H, Nakamura Y, Harigae H.
    • Organizer
      第82回日本血液学会総会
    • Related Report
      2020 Research-status Report
  • [Presentation] Characterization of congenital sideroblastic anemia model due to ABCB7 defects: How do defects in iron-sulfur cluster metabolism lead to ring sideroblast formation?2019

    • Author(s)
      Fujiwara T, Suzuki C, Ochi T, Ono K, Saito K, Fukuhara N, Onishi Y, Hisayuki Y, Fujimaki S, Nakamura Y, Harigae H
    • Organizer
      The 61th American Society of Hematology
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] EPIDEMIOLOGY AND MOLECULAR CHARACTERIZATION OF CONGENITAL SIDEROBLASTIC ANEMIA2019

    • Author(s)
      Fujiwara T, Saito K, Suzuki C, Ono K, Fukuhara N, Onishi Y, Nakamura Y, Harigae H
    • Organizer
      The 8th International Bioiron Society
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Proteomic analysis of mitochondrial membrane protein FAM210B in erythroid cells2019

    • Author(s)
      Suzuki C, Fujiwara T, Shima H, Saito K, Ono K, Fukuhara N, Onishi Y, Hisayuki Y, Fujimaki S, Nakamura Y, Harigae H
    • Organizer
      The 61th American Society of Hematology
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Molecular Characterization and Novel Therapeutic Strategy for X-linked Sideroblastic Anemia Associated with ALAS2 Missense Variants2019

    • Author(s)
      Ono K, Fujiwara T, Saito K, Suzuki C, Takahashi N, Onodera K, Ichikawa S, Fukuhara N, Onishi Y, Hisayuki Y, Nakamura Y, Harigae H
    • Organizer
      The 61th American Society of Hematology
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Ring sideroblast and iron metabolism2019

    • Author(s)
      Fujiwara T
    • Organizer
      The 81th Annual Meeting of the Japanese Society of Hematology
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] Generation and molecular characterization of human ring sideroblasts2018

    • Author(s)
      1.Saito K, Fujiwara T, Hatta S, Okitsu Y, Fukuhara N, Onishi Y, Nakamura Y, Harigae H
    • Organizer
      The 60th American Society of Hematology
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Characterization of in vitro model of X-linked sideroblastic anemia2018

    • Author(s)
      Saito K, Fujiwara T, Hatta S, Onodera K, Ichikawa S, Fukuhara N, Onishi Y, Nakamura Y, Harigae H
    • Organizer
      第80回日本血液学会総会
    • Related Report
      2018 Research-status Report
  • [Presentation] Establishment of a screening system to identify novel GATA-2 transcriptional regulators2018

    • Author(s)
      Ohashi K, Fujiwara T, Onodera K, Saito Y, Ichikawa S, Kobayashi M, Okitsu Y, Fukuhara N, Onishi Y, Harigae H
    • Organizer
      第80回日本血液学会総会
    • Related Report
      2018 Research-status Report
  • [Presentation] Cyclosporine A treatment for T-cell large granular lymphocyteic leukemia: a single-center experience2018

    • Author(s)
      Onishi Y, Fujiwara M, Sano S, Nakagawa R, Kawajiri A, Saito K, Onodera K, Ichikawa S, Fukuhara N, Fujiwara T, Harigae H
    • Organizer
      第80回日本血液学会総会
    • Related Report
      2018 Research-status Report
  • [Presentation] 鉄芽球性貧血の分子病態2018

    • Author(s)
      藤原 亨
    • Organizer
      第80回日本血液学会総会
    • Related Report
      2018 Research-status Report
    • Invited

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Published: 2018-04-23   Modified: 2023-01-30  

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