2005 Fiscal Year Final Research Report Summary
Investigation into the mechanism for expansion of abnormal clone in paroxysmal nocturnal hemoglobinuria
| Project/Area Number |
16590940
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Hematology
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| Research Institution | Osaka University |
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Principal Investigator |
MURAKAMI Yoshiko Osaka University, Research Institute for Microbial Diseases, Research associate, 微生物病研究所, 助手 (00304048)
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| Co-Investigator(Kenkyū-buntansha) |
KINOSHITA Taroh Osaka University, Research Institute for Microbial Diseases, Professor, 微生物病研究所, 教授 (10153165)
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| Project Period (FY) |
2004 – 2005
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| Keywords | PNH / HMGA2 / Eri1p / Ras |
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| Research Abstract |
Investigation into the mechanism for the benign tumor like proliferation of GPI negative hematopoietic stem cells.
We have analyzed two PNH patients who showed fully expanded GPI-deficient clones with similar chromosomal abnormalities. The high-mobility group protein A2 (HMGA2) is localized at the breakpoint and 3' UTR of HMGA2 is truncated in both patients (our unpublished data). The truncated form of HMGA2 is ectopically expressed in tumor tissues, unexpressed in normal state, and making cells grow like a benign tumor. We suggest that ectopic expression of this truncated HMGA2 or up-regulation of this target gene together with a PIG-A mutation result in expansion of GPI-deficient stem cells. In fact, HMGA2 was highly expressed only in the GPI negative populations of the bone marrow cells in both patients. However, HMGA2 expression was not significantly up-regulated in the peripheral blood cells in PNH patients including two patients mentioned above compared to normal individuals. We will further analyze the HMGA2 expression in the bone marrow samples. We have also made the transgenic mice of truncated form of HMGA2 and already confirmed its expression in bone marrow cells, so we are planning to investigate its relation to clonal expansion of PNH cells.
We have cloned PIG-Y, which is important for the first step enzyme complex in GPI biosynthesis. PIG-Y is the homologue of Eri1p of yeast, but we could not detect the interactions between PIG-Y and active form of Ras family proteins, which was proved in yeast system.
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