Host: The Japan Radiation Research Society
Co-host: Asian Association for Radiation Research
Increase of leukemia among atomic bomb survivors in Hiroshima and Nagasaki started from 1947, reached its peak around 1952, and continued until 1980s. By contrast, increase of myelodysplastic syndrome (MDS) continued even 60 years after the bombing. Many researchers believe that early onset leukemia after atomic bomb were caused primarily by chimeric genes as a result of chromosomal translocations, although there is no way to confirm it. Point mutations likely contribute to late onset MDS, while chromosomal deletions are implicated in both of them.
In this lecture, I show two topics. One is AML1 point mutations in MDS. We found that AML1 mutations in approximately 20% of 'preleukemic' MDS and/or AML precedent with MDS. This gene anomaly is found especially at high frequencies (40-50%) in MDS patients among atomic bomb survivors in Hiroshima and 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 candidate genes for chromosomal deletion in the long arm of chromosome 7, which is frequently observed in MDS and AML, especially in radiation-associated MDS/AML. We developed a unique microarray CGH system to detect micro-deletions and isolated a region which is commonly deleted in the MDS/AML patients at a high frequency. These candidate genes likely encode novel DNA-repair proteins and we are now concentrated to elucidate their function and implications in leukemogenesis.
