Pathological analysis of congenital hemolytic anemia due to mitochondrial selective autophagy disorder

2019 Fiscal Year Final Research Report

• Project/Area Number: 16K10041
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Tokyo Women's Medical University
• Principal Investigator: KANNO HITOSHI 東京女子医科大学, 医学部, 教授 (70221207)
• Co-Investigator(Kenkyū-buntansha): 小原 洋志 東京大学, 医科学研究所, 特任講師 (40528733)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Keywords: 溶血性貧血 / 無効造血

Outline of Final Research Achievements

A total of 255 cases of hemolytic anemia with undetermined causes were analyzed during the four years from 2015-2019. As a result, the disease type could be diagnosed in 188 cases (73.7%). Hereditary spherocytosis (HS) was the most common type, and dehydrated hereditary stomatocytosis (DHSt) was the second. The quantitative flow-cytometric osmotic fragility test (FCM-OF) was shown to be useful as a screening test for DHSt.
In erythroblasts derived from KLF1-CDA patients, the expression of γ-globin gene was significantly increased and the expression of 4.2 protein gene was also markedly decreased in comparison with the normal control. It was suggested that ineffective erythropoiesis was caused by multiple factors responsible for hemoglobin switching and erythrocyte cytoskeleton formation.

Free Research Field

遺伝医学

Academic Significance and Societal Importance of the Research Achievements

ヒト赤芽球の分化障害（無効造血）や成熟赤血球の早期細胞死（溶血）により様々な先天性貧血が発症する。我々は赤血球膜・酵素・ヘモグロビンなどの異常により発症する先天性溶血性貧血の病因解析を実施し、その74％に病因を確定出来た。本研究では無効造血や溶血の病因解析のための網羅的遺伝子解析システムを構築し、患者iPS細胞から分化した赤芽球を用いた病因解析を実施した。脱水型遺伝性有口赤血球症(DHSt)が遺伝性球状赤血球症に次いで頻度の高い先天性溶血性貧血であることを明らかにし、迅速診断法としてフローサイトメトリーを用いた定量的赤血球浸透圧脆弱性試験（FCM-OF）が有用であることを示した。