Evidence suggests that de novo,
therapy-related and
benzene-induced
acute myeloid leukemias (AML) occur via similar cytogenetic and genetic pathways, several of which involve
aneuploidy, the loss or gain of chromosomes.
Aneuploidy of specific chromosomes has been detected in
benzene-related
leukemia patients as well as in healthy
benzene-exposed workers, suggesting that
aneuploidy precedes and may be a potential mechanism underlying
benzene-induced
leukemia. Here, we analyzed the peripheral blood lymphocytes of 47 exposed workers and 27 unexposed controls using a novel OctoChrome fluorescence in situ hybridization (FISH) technique that simultaneously detects
aneuploidy in all 24 chromosomes. Through this chromosome-wide
aneuploidy study (CWAS) approach, we found heterogeneity in the
monosomy and
trisomy rates of the 22 autosomes when plotted against continuous
benzene exposure. In addition, statistically significant, chromosome-specific increases in the rates of
monosomy [5, 6, 7, 10, 16 and 19] and
trisomy [5, 6, 7, 8, 10, 14, 16, 21 and 22] were found to be dose dependently associated with
benzene exposure. Furthermore, significantly higher rates of
monosomy and
trisomy were observed in a priori defined 'susceptible' chromosome sets compared with all other chromosomes. Together, these findings confirm that
benzene exposure is associated with specific chromosomal
aneuploidies in hematopoietic cells, which suggests that such
aneuploidies may play roles in
benzene-induced leukemogenesis.