Abstract 2994: Benzene induces leukemia-related chromosome loss in myeloid progenitor cells

Benzene, a common environmental pollutant, is an established cause of acute myeloid leukemia (AML) and other blood disorders, such as myelodysplastic syndromes (MDS). However, the precise mechanisms by which it produces leukemia and related disorders remain unclear. Previously, we reported that benzene exposure, at and below the current US occupational standard of 1 ppm, significantly reduced essentially all types of peripheral blood cell counts in shoe workers in China (Lan et al, 2004). This suggests a toxic effect of benzene on bone marrow since all peripheral blood cells arise from stem and early progenitor cells located in the bone marrow, which are also the target cells for leukemia induction. A portion of these stem and early progenitor cells circulate in the blood making it possible to measure their proliferation potential. We previously showed that colony formation from blood myeloid progenitor cells (including CFU-GM and CFU-GEMM) significantly declined with increasing benzene exposure and was more sensitive to the effects of benzene than was the number of mature blood cells (Lan et al, 2004). We have now investigated the effect of different levels of benzene exposure on the loss and gain of chromosomes 7 and 8, as these are the most common cytogenetic changes observed in AML and MDS and are thought to be causally related to the disease process. CFU-GM cells were cultured in methylcellulose colony-forming assays (StemCell Technologies) from a subset (n = 42) of the workers studied previously (18 workers exposed to 10 ppm benzene and 14 unexposed controls) for cytogenetic analysis by interphase FISH (fluorescence in situ hybridization) microscopically. Here, we report that benzene exposure above and below 10 ppm caused significant increases in the loss (monosomy) of chromosomes 7 and 8 in comparison to controls and that the trend with increasing exposure was significant (ptrend < 0.01). The gain (trisomy) of both chromosomes 7 and 8 was not significantly affected by benzene exposure in the 42 subjects studied here. In conclusion, interphase cytogenetic analysis of the loss of chromosomes 7 and 8 in myeloid progenitors is a potential biomarker for the effects of benzene exposure in humans. Further, our results support the idea that the loss of chromosome 7 in early myeloid progenitor cells is a probable mechanism contributing to benzene-induced AML and MDS. Supported by NIEHS-NIH grant RO1-ES06721 and Intramural Funds from NCI. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2994.