The Japan Radiation Research Society Annual Meeting Abstracts
The 50th Annual Meeting of The Japan Radiation Research Society
Session ID : X4-3
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Joint Symposium of Hiroshima University 21st Century COE Program and Nagasaki University Global COE Program
Recent advances in molecular oncogenesis of radiation-associated myelodysplastic syndrome (MDS).
*Toshiya INABA
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Keywords: MDS, AML1, Miki
CONFERENCE PROCEEDINGS FREE ACCESS

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Abstract
The elevated risk of leukemia among atomic bomb survivors appeared from 1947, reached its peak around 1952, and continued until 1960s. By contrast, recent studies suggested that increased incidence of myelodysplastic syndrome (MDS), so-called preleukemia or smoldering leumkemia, continues even 60 years after the bombing. It is generally accepted that the early onset leukemia are caused primarily by chimeric genes as a result of chromosomal translocations, whereas point mutations and/or chromosomal deletions likely contribute to the late onset MDS.
Two genes that would be involved in the development of radiation-associated MDS were identified recently in our laboratory. First, mutations of AML1/RUNX1, a transcription factor indispensable for the definitive hematopoiesis, were found in approximately 20% of sporadic MDS. AML1 mutations were found especially at high frequencies (40-50%) in MDS patients among atomic bomb survivors in Hiroshima, as well as in radiation-associated MDS/AML patients. Moreover, mutations in radiation-associated MDS were limited to the runt-homology domain, which mediates DNA binding, while those in sporadic MDS patients distributed throughout AML1 protein. Second, we isolated a candidate gene, Miki(mitotic kinetics regulator) from the long arm of chromosome 7, which is frequently deleted in radiation-associated MDS and AML (up to 50%), as well as in sporadic cases (5-20%). Downregulation of Miki induced severe mitotic defect and abnormal morphology similar to those in bone marrow cells of MDS patients, suggesting that deletion of Miki gene would contibutes to development and/or progression of MDS.
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© 2007 The Japan Radiation Research Society
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