Identification of predictors of response to thrombopoietin receptor agonists in refractory aplastic anemia

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K08318
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54010:Hematology and medical oncology-related
• Research Institution: Kanazawa University
• Principal Investigator: Yamazaki Hirohito 金沢大学, 附属病院, 准教授 (50361994)
• Project Period (FY): 2018-04-01 – 2021-03-31
• 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

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.

Free Research Field

血液内科学

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。