Elucidation of molecular epidemiology and pathophysiology of acquired sideroblastic anemia
Project/Area Number |
18K08314
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 54010:Hematology and medical oncology-related
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Research Institution | Tohoku University |
Principal Investigator |
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Project Period (FY) |
2018-04-01 – 2022-03-31
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Project Status |
Completed (Fiscal Year 2021)
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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)
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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.
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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。
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Report
(5 results)
Research Products
(35 results)
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[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
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Journal Title
The Tohoku Journal of Experimental Medicine
Volume: 249
Issue: 1
Pages: 19-28
DOI
NAID
ISSN
0040-8727, 1349-3329
Related Report
Peer Reviewed / Open Access
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[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.
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Journal Title
Ann Hematol.
Volume: -
Issue: 8
Pages: 1999-2001
DOI
Related Report
Peer Reviewed
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[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.
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Journal Title
Mol Cell Biol.
Volume: 39
Issue: 7
DOI
Related Report
Peer Reviewed
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[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
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Journal Title
Nat Immunol
Volume: 19
Issue: 10
Pages: 496-497
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[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
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[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
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[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
Int'l Joint Research
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[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
Int'l Joint Research
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[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
Int'l Joint Research
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[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
Int'l Joint Research
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[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
Int'l Joint Research
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[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
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[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
Int'l Joint Research
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[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
Int'l Joint Research
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[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
Int'l Joint Research
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[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
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