Radiation leukemogenesis: a proteomic approach

The objectives of this study were to identify protein biomarkers of radiation-induced acute myeloid leukemia (rAML) in CBA/CaJ mice, and to examine the similarities or differences in the patterns of protein-expression profiles among AMLs induced by low linear energy transfer (LET) radiation (e.g., gamma- or x-rays), and high LET radiation (i.e., neutrons).

We used two-dimensional electrophoresis gel in combination with mass spectrometry (MS), i.e., matrix-assisted laser desorption ionization/time-of-flight MS and electrospray ionization-liquid chromatography/tandem mass spectrometry, to identify protein signatures in blood-plasma samples collected from control and rAML mice. There were nine cases of rAML (three cases induced by high LET radiation; six induced by low LET radiation) and eight control mice at similar ages.

The results showed differences in the patterns of protein profiles from blood-plasma samples collected from rAML vs control mice. Moreover, our data demonstrated, both qualitatively and quantitatively, differences between the plasma protein profiles obtained from mice with AML induced by low vs high LET radiation. Most of the proteins that were present at greater levels in normal samples than in rAML samples were associated with normal metabolism and growth. Several acute-phase proteins were upregulated in rAML samples.

The data present, for the first time, evidence for increased expression of clusterin and a loss of gelsolin expression in blood plasma as potential biomarkers of rAML in the CBA/CaJ mouse. Results also indicate that two-dimensional electrophoresis, in combination with MS, is a highly sensitive technique for identification of blood-based biomarkers of rAML.