MLL leukemia-associated rearrangements in peripheral blood lymphocytes from healthy individuals

Chromosomal translocations are characteristic of hematopoietic neoplasias and can lead to unregulated oncogene expression or the fusion of genes to yield novel functions. In recent years, different lymphoma/leukemia-associated rearrangements have been detected in healthy individuals. In this study, we used inverse PCR to screen peripheral lymphocytes from 100 healthy individuals for the presence of MLL (Mixed Lineage Leukemia) translocations. Forty-nine percent of the probands showed MLL rearrangements. Sequence analysis showed that these rearrangements were specific for MLL translocations that corresponded to t(4;11)(q21;q23) (66%) and t(9;11) (20%). However, RT-PCR failed to detect any expression of t(4;11)(q21;q23) in our population. We suggest that 11q23 rearrangements in peripheral lymphocytes from normal individuals may result from exposure to endogenous or exogenous DNA-damaging agents. In practical terms, the high susceptibility of the MLL gene to chemically-induced damage suggests that monitoring the aberrations associated with this gene in peripheral lymphocytes may be a sensitive assay for assessing genomic instability in individuals exposed to genotoxic stress

Three-dimensional characterization of the permeability of W–Cu composites using a new “TriBeam” technique

Large three-dimensional microstructural datasets have been gathered for two W–Cu composites of 10 and 15 wt.% Cu using the TriBeam system via in situ femtosecond laser sectioning in a scanning electron microscope. Laser ablation was performed on W–Cu samples along a 90 ° edge, milling parallel with the imaging surface. Secondary electron images for 1000 two-dimensional slices were segmented into binary images representing Cu and W components using EM/MPM (expectation–maximization/maximization of the posterior marginals) image-processing algorithms. A statistically random volume sampling approach has been employed to evaluate the microstructural and property volume element sizes necessary for the assessment of volume fraction, surface-area to volume ratio and permeability, respectively. This approach also characterizes the mean values and variability in microstructure and properties for volume elements ranging from 10 μm to 160 μm on edge. The converged values of the volume fractions of Cu closely match experimental values measured by the Archimedes technique.© 2013 Acta Materialia Inc