Wilms' tumor 1 (WT1) gene in hematopoiesis: A surrogate marker of cell proliferation as a possible mechanism of action?

Background: Wilms' tumor 1 (WT1) gene expression is seen in a significant number of cases of human neoplasia; however the mechanism of action remains to be clarified. We hypothesized that WT1 gene is a surrogate marker of proliferation in normal hematopoietic cells and leukemias. While we and others have recognized its value as a tool for the detection of minimal residual disease (MRD), the objective of this study was to confirm our hypothesis regarding normal. Methods: Samples from healthy donors (n = 16) and UC blood (n = 9) were cultured in Methocult™ for 21 days. Colonies were analyzed on days 7, 14 and 21 by RT-PCR for WT1 gene expression. Our positive controls were ramples from patients with leukemia (n = 91). Negative controls were from normal volunteers without stimulation (n = 26). Results: Results showed a statistically significant difference (P < 0.0001) between cultured groups, with the highest level of WT1 gene expression in the positive controls and on day 14, when cells are at their maximal proliferation. Discussion: In conclusion, WT1 gene expression in the proliferating colonies was highest on day 14, although less than in leukemia samples, confirming our hypothesis that WT1 gene is a surrogate marker of proliferation, not only in leukemogenesis but also, to a lesser degree, in normal cell proliferation.