Analysos of metabolic abnormality which causes clonal expansion in Paroxysmal nocturnal hemoglobinuria

2016 Fiscal Year Final Research Report

• Project/Area Number: 15K15362
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Hematology
• Research Institution: Osaka University
• Principal Investigator: Murakami Yoshiko 大阪大学, 微生物病研究所, 准教授 (00304048)
• Co-Investigator(Renkei-kenkyūsha): Kinoshita Taroh 大阪大学, 微生物病研究所, 教授 (10153165) ; Inoue Norimitsu 大阪府立成人病センター, 部門長 (80252708) ; Nishimura Junichi 大阪大学, 医学部, 助教 (80464246)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Keywords: アルカリホスファターゼ / ビタミンB１ / ビタミンB６ / 発作性夜間ヘモグロビン尿症 / GPI アンカー / clonal expansion / PIGA

Outline of Final Research Achievements

Paroxysmal Nocturnal hemoglobinuria (PNH) is the hematopoietic disease caused by the somatic mutation of PIGA gene. PIGA is essential enzyme for biosynthesis of GPI anchor, which anchor the various GPI anchored protein to the cell surface. So, PIGA deficient cells will be GPI negative cells. These GPI negative cells expand, however, the mechanism of which is unknown. Alkaline phosphatase (ALP) is one of the GPI-anchored proteins and it is defective in GPI negative cells. ALP is involved in taking up the vitamins into the cells and defect in ALP causes deficiency of vitamins in the cells, leading to various metabolic abnormalities. We speculate this causes clonal expansion of GPI negative cells. Analysis of concentration of vitamins in the cells or serum of the model mice indicated that mutant mice showed decrease in taking up vitamins.

Free Research Field

分子生物学・血液学