Therapeutic Strategies and Biomarkers for Graft Failure in Allogenic Hematopoietic Cell Transplantation

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K08422
• 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: Fukushima Medical University
• Principal Investigator: Ogawa Kazuei 福島県立医科大学, 保健科学部, 教授 (40423800)
• Co-Investigator(Kenkyū-buntansha): 大河原 浩 福島県立医科大学, 医学部, 准教授 (10381360) ; 深津 真彦 福島県立医科大学, 医学部, 助手 (30827829) ; 池添 隆之 福島県立医科大学, 医学部, 教授 (80294833)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 同種造血幹細胞移植 / 生着不全 / Mer / Gas6

Outline of Final Research Achievements

To generate the mice with graft failure after AHSCT, we performed experimental AHSCT using B6 donor mice and BALB/C recipient mice. Despite the different MHC classes and leukocyte allotypes, graft failure (GF) was not induced. Thus, we examined whether pseudoviral infection (administration of poly I:C) could induce the graft failure. In the bone marrow of mice with GF histological analysis showed that the cell density of hematopoietic nests was significantly decreased. The levels of ROS production were in the bone marrow significantly increased. In addition, M1-type activated macrophages, which contribute to hemophagocytosis, were significantly increased in the bone marrow of the mice with GF. TAM family Mer inhibitor significantly suppressed the onset of GF, suggesting that Mer may play an important role in the pathogenesis of GF.

Free Research Field

血液内科学

Academic Significance and Societal Importance of the Research Achievements

同種造血幹細胞移植 (HSCT)は抗癌剤抵抗性の造血器悪性腫瘍の唯一の根治治療である。HSCT患者の生命予後を左右する合併症に生着不全(graft failure, GF) がある。GFのリスク因子はHLA適合度、ドナー低CD34+細胞数、骨髄非破壊的前処置、再生不良性貧血等の非腫瘍性疾患、脾腫、骨髄線維症の有無、ウイルス感染等が挙げられる。GFの発生機序の詳細は未だ明らかではない。本研究成果は生着不全の発症機序を明らかにし、HSCTの成功率や治療成績の向上に寄与する。