Effect of heme oxygenase-1 on treatment results after hematopoietic stem cell transplantation and new therapeutic strategies

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K07442
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52010:General internal medicine-related
• Research Institution: Kanazawa University
• Principal Investigator: Morishita Eriko 金沢大学, 保健学系, 教授 (50251921)
• Co-Investigator(Kenkyū-buntansha): 谷内江 昭宏 金沢大学, 附属病院, 特任教授 (40210281)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: HO-1 / 同種造血幹細胞移植 / 移植片対宿主病 / 血栓性微小血管障害症 / 一塩基多型（SNP) / ADAMTS-13 / UNC-93 homolog B1

Outline of Final Research Achievements

Life-threatening complications associated with allogeneic hematopoietic stem cell transplantation (SCT),such as severe infection, graft-versus-host disease (GVHD), and thrombotic microangiopathy, remain obstacles to overcome. We investigated the influence of the HO-1 single-nucleotide polymorphism (SNP) rs2071746 (-413A>T), ADAMTS-13 SNP rs2285489 (C>T), UNC-93 homolog B1 SNP rs308328 (T>C) on transplant outcomes in a cohort of about 600 patients undergoing unrelated HLA-matched bone marrow transplantation (BMT) for hematologic malignancies through the Japan Marrow Donor Program.
As a result, the donor HO-1 A/A or A/T genotype and donor UNC93B1 C/C genotype were associated with a better overall survival. On the other hand, the recipient ADAMTS13 C/C genotype was associated with an increased relapse rate, resulting in a lower disease-free survival rate in the patients with a recipient C/C genotype.

Free Research Field

血栓止血

Academic Significance and Societal Importance of the Research Achievements

同種造血幹細胞移植(SCT)は、造血器悪性腫瘍を完治する治療法として期待されているが、重症感染症や移植片対宿主病、血栓性微小血管障害症などの移植後合併症はいまだ致死率も高い。これらの病態には免疫応答や血液凝固系の関与が考えられており、今回の検討でも免疫調節性あるいは抗血栓性非HLA遺伝子多型が移植後転帰に影響を与えることが明らかになってきた。したがって、これらの因子の遺伝子型の分析は、ドナーの選択、予後の推定、および同種SCT後の治療戦略の作成に役立つ可能性が示された。