Polymorphism in the human flavin-containing quinine reductase, NQO1, corresponds to rapid degradation and the absence or only trace levels of NQO1. Reduced NQO1 has been associated with a variety of de novo and therapy-induced leukemia as well as increased risk of myeloid toxicity after benzene exposure. The study by Zhou et al. investigates the role of NQO1 depletion on adhesion molecule expression and the resulting functional deficit in adhesion. Inhibition or knockdown of NQO1 in transformed human bone marrow endothelial cells resulted in a significant reduction in tumor necrosis factor-α-induced E-selectin, vascular cell adhesion molecule-1, and intercellular adhesion molecule-1 expression that manifested as a functional deficit in adhesion of CD34+ cells to these transformed endothelial cells. Alterations in adhesive ability of these transformed endothelial cells may affect the function of the vascular stem cell niche contributing to the susceptibility of these polymorphic individuals to leukemia and hematotoxicants.
See article at J Pharmacol Exp Ther 2010, 334:260–268.
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