Identification of predictors of response to thrombopoietin receptor agonists in refractory aplastic anemia
Project/Area Number |
18K08318
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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 | Kanazawa University |
Principal Investigator |
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Project Period (FY) |
2018-04-01 – 2021-03-31
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Project Status |
Completed (Fiscal Year 2020)
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Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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Keywords | 再生不良性貧血 / トロンボポエチン受容体作動薬 / HLAクラスⅠアリル欠失血球 / GPIアンカー型蛋白欠失血球 / エルトロンボパグ / ロミプロスチム / GPIアンカー膜蛋白欠失血球 / HLAクラスⅠアレル欠失血球 / 細胞表面抗原解析 / TPO受容体作動薬 |
Outline of Final Research Achievements |
To gain insight into the origin of HLA class I allele-lacking (HLA[-]) and GPI-anchored membrane protein-deficient (GPI[-]) cells and mechanisms underlying escape of these marker(-) hematopoietic stem cells (HSCs) in patients with acquired aplastic anemia (AA), we analyzed the lineage diversity of these marker(-) cells using flow cytometry. Our study revealed that the HLA lacking occurred in more immature hematopoietic stem cells (HSCs) than HSCs with PIGA mutations. The percentage of HLA(-) granulocytes continued to increase in patients in remission off cyclosporine (CsA), suggesting that the cytotoxic T cell (CTL) attack against HSCs persists even after AA patients achieved remission not requiring CsA. On the other hand, mechanisms other than immune attack by CTLs was suspected to be involved in the survival advantage of PIGA mutated HSCs.
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Academic Significance and Societal Importance of the Research Achievements |
治療抵抗性の特発性再生不良性貧血に対して、40~50%の奏効が得られるエルトロンボパグ(EPAG)の登場は、再生不良性貧血診療を大きく進展させた。しかし、一部の症例に治療前には認めなかった新たな染色体異常が出現することが明らかとなり、治療開始を躊躇う例も見受けられる。そのため、EPAGの効果予測マーカーを同定することは、適切な治療を迅速に選択するためにも重要である。
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Report
(4 results)
Research Products
(24 results)
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[Journal Article] HLA class I allele-lacking leukocytes predict rare clonal evolution to MDS/AML in patients with acquired aplastic anemia.2021
Author(s)
Hosokawa K, Mizumaki H, Yoroidaka T, Maruyama H, Imi T, Tsuji N, Urushihara R, Tanabe M, Zaimoku Y, Nguyen MAT, Tran DC, Ishiyama K, Yamazaki H, Katagiri T, Takamatsu H, Hosomichi K, Tajima A, Azuma F, Ogawa S, Nakao S.
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Journal Title
Blood
Volume: -
Issue: 25
Pages: 3576-3580
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Hematopoietic stem progenitor cells lacking HLA differ from those lacking GPI-anchored proteins in the hierarchical stage and sensitivity to immune attack in patients with acquired aplastic anemia2021
Author(s)
Yoroidaka T, Hosokawa K, Imi T, Mizumaki H, Katagiri T, Ishiyama K, Yamazaki H, Azuma F, Nanya Y, Ogawa S, Nakao S
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Journal Title
Leukemia
Volume: in press
Issue: 11
Pages: 3257-3267
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Hematologic recovery induced by eltrombopag in Japanese patients with aplastic anemia refractory or intolerant to immunosuppressive therapy.2019
Author(s)
Yamazaki H, Ohta K, Iida H, Imada K, Obara N, Tokumine Y, Tomiyama Y, Usuki K, Imajo K, Miyamura K, Sasaki O, Fanghong Z, Hattori T, Tajima T, Matsuda A, Nakao S.
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Journal Title
Int J Hematol
Volume: 110
Issue: 2
Pages: 187-196
DOI
Related Report
Peer Reviewed
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[Journal Article] Prospective randomized trial comparing two doses of rabbit anti-thymocyte globulin in patients with severe aplastic anaemia.2019
Author(s)
Narita A, Zhu X, Muramatsu H, Chen X, Guo Y, Yang W, Zhang J, Liu F, Jang JH, Kook H, Kim H, Usuki K, Yamazaki H, Takahashi Y, Nakao S, Wook Lee J, Kojima S
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Journal Title
Br J Haematol
Volume: 187
Issue: 2
Pages: 227-237
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Presentation] Clonal Hematopoiesis By HLA Class I Allele-Lacking Hematopoietic Stem Cells and Concomitant Aberrant Stem Cells Is Rarely Associated with Clonal Evolution to Secondary Myelodysplastic Syndrome and Acute Myeloid Leukemia in Patients with Acquired Aplastic Anemia2020
Author(s)
Kohei Hosokawa, Hiroki Mizumaki, Takeshi Yoroidaka, Hiroyuki Maruyama, Tatsuya Imi, Noriaki Tsuji, Ryota Urushihara, Mikoto Tanabe, Yoshitaka Zaimoku, Mai Anh Thi Nguyen, Dung Cao Tran, Ken Ishiyama, Hirohito Yamazaki, Takamasa Katagiri, Kazuyoshi Hosomichi, Atsushi Tajima, Fumihiro Azuma, Seishi Ogawa, Shinji Nakao
Organizer
The 62th ASH annual meeting
Related Report
Int'l Joint Research
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[Presentation] The high NK cell count at diagnosis predicts a good response to IST in aplastic anemia2019
Author(s)
Atsushi Narita, Hideki Muramatsu, Yinyan Xu, Motoharu Hamada, Daisuke Ichikawa, Eri Nishikawa, Nozomu Kawashima, Yusuke Okuno, Nobuhiro Nishio, Hirohito Yamazaki, Shinji Nakao, Seiji Kojima, Yoshiyuki Takahashi
Organizer
第81回日本血液学会学術集会
Related Report
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[Presentation] Limited class I HLAs are involved in the auto-antigen presentation in acquired aplastic anemia2018
Author(s)
Mikoto Tanabe, Hiroki Mizumaki, Tatsuya Imi, Takeshi Yoroidaka, Noriharu Nakagawa, Ken Ishiyama, Hirohito Yamazaki, Yoshiraka Zaimoku, Takamasa Katagiri, Kazuyoshi Hosomichi, Atsushi Tajima, Shinji Nakao
Organizer
第80回日本血液学会学術集会
Related Report
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[Presentation] Familial acquired aplastic anemia diagnosed by aberrant leukocytes that lacked common HLA alleles2018
Author(s)
Tatsuya Imi, Ryosuke Ogawa, Kazuyoshi Hosomichi, Hiroki Mizumaki, Noriharu Nakagawa, Takeshi Yoroidaka, Mikoto Tanabe, Noriaki Tsuji, Kohei Hosokawa, Hiroyuki Takamatsu, Ken Ishiyama, Yukio Kondo, Hirohito Yamazaki, Atsushi Tajima, Shinji Nakao
Organizer
第80回日本血液学会学術集会
Related Report
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[Presentation] Response to IST in PNH(+) BMF patients with a history of chemo- or radiotherapy2018
Author(s)
Noriharu Nakagawa, Mikoto Tanabe, Ishikazu Mizuno, Satoshi Morishige, Shuji Matsuzawa, Takahiko Ito, Masahiko Sumi, Nobuyuki Takayama, Ken Ishiyama, Hirohito Yamazaki, Shinji Nakao
Organizer
第80回日本血液学会学術集会
Related Report
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