Mutation of PIG-A gene during differentiation from hematopoietic progenitors in paroxysmal nocturnal hemoglobinuria

阵发性睡眠性血红蛋白尿症造血祖细胞分化过程中 PIG-A 基因突变

• 批准号: 07671226
• 负责人: KANAMARU Akihisa
• 金额: $ 1.28万
• 依托单位: Hyogo College of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07671226/
• 关键词: PNH; PIG-A gene; hematopoietic progenitors; GPI-anchor; CD59; PIG-A遺伝子

Recent studies indicate that the GPI-anchor biosynthesis is associated with PIG-A gene. A variety of mutation (s) of this gene has been found in every patients with paroxysmal nocturnal hemoglobinuria (PNH). We studied on the mutation of PIG-A gene during the differentiation from hematopoietic progen itors in PNH.Non-phagocytic mononuclear cells were prepared from the patients with PNH after obtaining the informed consent, and cultured in methylcellulose for 10-14 days. Individual colonies/bursts were picked up and divided into two fractions for the analyzes of CD59 expression and PIG-A gene status. We have obtained 4 groups of colonies/bursts ; each group of CD59+with normal PIG-A,CD59+with mutated PIG-A,CD59- with normal PIG-A,and CD59- with mutated PIG-A.A group of CD59+ with normal PIG-A and that of CD59- with mutated PIG-A might be normal and the PNH clone, respectivelly. Mutation (s) may be found in other region of the gene for the colonies/bursts of CD59- with normal PIG-A group. However, there is a discordance between the expression of GPI-anchored proteins and PIG-A mutation in the group of CD59+ with mutated PIG-A.It is speculated that another pathway bypassing PIG-A gene is in operation for the GPI-anchor biosynthesis.

最近的研究表明，GPI锚生物合成与PIG-A基因有关。在阵发性夜间血红蛋白尿（PNH）的每个患者中都发现了该基因的多种突变。我们研究了PNH中与造血祖迭代者分化过程中PIG-A基因的突变。在获得知情同意后，从PNH患者中制备了pNH-Phagococytic单核细胞，并在甲基纤维素中培养10-14天。单个菌落/爆发被捡起并分为两个部分，以分析CD59表达和PIG-A基因状态。我们获得了4组菌落/爆发；每组CD59+具有正常PIG-A，CD59+的CD59+，具有突变的PIG-A，CD59-具有正常PIG-A，CD59-具有突变的PIG-A.A组CD59+的CD59+，带有正常PIG-A，CD59-具有突变的CD59- Pig-A可能是正常的，并且PNH克隆，分别是。可以在基因的其他区域中发现突变的CD59的菌落/爆发与正常的PIG-A组。然而，与突变的pig-a的CD59+组中GPI锚定蛋白的表达与PIG-A突变之间存在不一致。 。

项目成果

T.Nishimura,A.Kanamaru,et al.: "Flow cytometric analysis of homologous restriction factor 20KD(HRF20) expression on progeny cells during differentiation from hemopoietic progeniotrs in PNH" Br J Haematol. 90. 293-299 (1995)

T.Nishimura、A.Kanamaru 等人：“PNH 造血祖细胞分化过程中子代细胞同源限制因子 20KD (HRF20) 表达的流式细胞术分析”Br J Haematol。

金丸昭久 他: "発作性夜間血色素尿症(PNH)における造血幹細胞の分化とGPIアンカー膜蛋白発現" 日本内科学会雑誌. 85. 1160-1164 (1996)

Akihisa Kanamaru 等人：“阵发性夜间血红蛋白尿 (PNH) 中造血干细胞的分化和 GPI 锚定膜蛋白的表达”日本内科学会杂志 85. 1160-1164 (1996)。