The analysis of heme synthesis mechanism and the establishment of disease model cells for X-linked sideroblastic anemia using an immortalized human erythroid cell line.

2016 Fiscal Year Final Research Report

• Project/Area Number: 15K19539
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Hematology
• Research Institution: Iwate Medical University
• Principal Investigator: Kaneko Kiriko 岩手医科大学, 医学部, 講師 (10545784)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Keywords: ヘム合成 / 鉄代謝 / 赤芽球分化

Outline of Final Research Achievements

Erythroid-specific 5-aminolevulinate synthase (ALAS2) is the rate-limiting enzyme of heme biosynthetic pathway in erythroid cells. The mutation of ALAS2 gene causes X-linked sideroblastic anemia (XLSA). The aim of this project is to clarify the pathogenic mechanism of ALAS2-mutated XLSA in erythroid cells, and we tried to establish model cells. We have introduced the mutation, which disrupt the ALAS2, into the genome DNA of human erythroid progenitor cells using CRISPR/Cas9 system. The accumulation of iron was increased and showed circular pattern around the nucleus during the erythroid differentiation of ALAS2-deficient cells. Since the occurrence of ringed sideroblast was equal to diagnostic criterion for sideroblastic anemia, the established cells were considered available for model cells of XLSA. We believe that our disease model cells will be able to provide a lot of valuable information related to the cellular background for the formation of ring sideroblasts.

Free Research Field

赤芽球分化