SCREENING FOR THE GENES RESPONSIBLE FOR THE SURVIVAL ADVANTAGE OF PNH CLONES

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Somatic mutations in the PIG-A gene have been found in all PNH cases. Therefore PIG-A gene mutation has been considered to be responsible for the development of PNH. However, recent study revealed that rare PNH cells are present also in healthy individuals (Araten, DJ et al. 1996). Therefore, it is postulated that growth advantage and/or survival advantage of PNH clones is indispensable for the development of PNH, in addition to PIG-A gene mutation. The purpose of this study is to clarify the genes concerned in growth advantage and/or survival advantage of PNH clones. We performed a cDNA subtraction and a cDNA macro array to screen for the genes up-regulated in CD59^- granulocytes of PNH patient compared to CD59^+ granulocytes of PNH patient. Three genes were up-regulated more than 2 times in CD59^- granulocytes of one PNH patient by semi-quantitative RT-PCR assay. However we could not find remarkable tendency that these genes are up-regulated in CD59^- granulocytes compared to CD59^+ granulocytes in 3 other PNH patients. Already, 4 genes were reported up-regulated in PNH patients before. We have checked the expression of these 4 genes in 7 PNH patients and in 5 healthy donors by semi-quantitative RT-PCR. We could not find tendency that these 4 genes were up-regulated in our PNH patients.