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

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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.