Distribution of chromosome breakpoints in benzene-exposed and unexposed AML patients

Results of laboratory studies and investigations of occupationally exposed healthy individuals have been used to develop a mode of action for benzene-induced leukemia that mirrors disease following treatment with chemotherapeutic agents. Recently we have described series of AML and MDS cases with benzene exposure history, and have provided cytogenetic, molecular, and pathologic evidence that these cases differ significantly in many features from therapy-related disease. Here we have extended this work, and describe chromosome breakpoints across 441 identifiable regions, in terms of gains or losses, in 710 AML cases collected during the Shanghai Health Study, which include 75 with a history of benzene exposure. Using FISH and cytogenetic analysis, we developed prevalence information and risk ratios for benzene exposure across all regions with a lesion in at least one exposed and unexposed case. These results indicate that AML following benzene exposure mirrors de novo disease, and supports a mechanism for development of hematopoietic disease that bears no resemblance to therapy-related disease.