Host: The Japan Radiation Research Society
Co-host: Asian Association for Radiation Research
We previously reported that the relative risk of MDS among Hiroshima A bomb survivors was 2.53 at 1 Sv between 1985 and 1999. In order to clarify the molecular mechanism of MDS genesis including radiation-associated MDS, we studied the point mutations of AML1/RUNX1. AML1 point mutations were frequently detected in both sporadic and secondary MDS/AML(RAEB, RAEBt and MDS derived AML), while rarely detected in RA and RARS. The frequency was 17% (15/88) in sporadic MDS/AML and 50% (11/22) in secondary MDS/AML. Each 7 and 8 of 15 mutations in sporadic MDS/AML were localized in N-terminal (including Runt homology domain) and C-terminal region of AML1, respectively, whereas 10 of the 11 mutations in secondary MDS/AML were in N-terminal region. The majority of the AML1 mutants lost the trans-activation potential. In AML1-mutated MDS/AML cases, cytogenetically normal karyotype, -7/7q-, +8 and -5/5q- were observed in 42%, 29%, 23% and 0%, respectively. The additional mutations were detected in 38 % of these cases, including RAS pathway genes, c-kit, FLT-3 and p53. These results suggested that AML1 point mutations, in cooperation with additional genetic changes, play a major role in the development of MDS/AML, especially in secondary MDS/AML.
