International collaborative effort to study of pathophysiology and development of novel therapy of congenital sideroblastic anemia

2019 Fiscal Year Final Research Report

• Project/Area Number: 17H04668
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 海外学術
• Research Field: Hematology
• Research Institution: Tohoku University
• Principal Investigator: Harigae Hideo 東北大学, 医学系研究科, 教授 (50302146)
• Co-Investigator(Kenkyū-buntansha): 梨井 康 国立研究開発法人国立成育医療研究センター, 移植免疫研究室, 室長 (60321890)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 鉄芽球性貧血

Outline of Final Research Achievements

As congenital sideroblastic anemia (CSA)is very rare, there is a need to collect the data of patients and clarify the molecular pathogenesis to develop a novel therapy by the international collaborative study. In this study, 17 cases of congenital sideroblastic anemia were found at Chinese Academy of Medical Sciences and Peking Union Medical College. In 7 out of 17cases, mutations of 5-aminolevulinate synthase (ALAS2) gene, which is the first enzyme of heme biosynthesis in erythroid cells were identified. In addition, mutations of SLC25A38 gene, which codes the mitochondrial glycine transporter were identified in 3 out of 17cases. Gene mutations of 22 congenital anemia cases at National Institute of Immunohaematology in India were analyzed; however, mutations responsible for CSA were not identified. In Japan, a novel mutation of HSPA9 gene and SLC5A6 gene was found. The significance of mutations are being confirmed by in vitro differentiation system established in this study.

Free Research Field

血液内科学

Academic Significance and Societal Importance of the Research Achievements

遺伝性鉄芽球性貧血はミトコンドリアにおける鉄代謝に異常が生じ発症する難治性貧血である。極めてまれな疾患で、新たな治療法の開発には国際間での症例の蓄積が必要である。本研究によって、中国・インドにおいても症例数が限られていることが明らかとなった。一方で、中国で確認された症例の遺伝子変異は日本でのそれと類似していることが確認できた。また、本邦においても新たな候補遺伝子が確認され、本研究で確立したin vitroのモデル系で検証中である。本研究で国際的な共同研究体制が確立できたこと、またin vitroでのモデル系が確立できたことは極めて学術的・社会的に意義があると思われる。