miR-494 and miR-320a expression in leukemia samples, and a model of action. (A) RNA was isolated from diagnostic leukemia samples from 11 TEL-AML1 positive and 15 TEL-AML1 negative cALL patients, and miRNA expression for miR-494 and miR-320a were analyzed by quantitative PCR. Shown are box-and-whisker plots of log10-transformed data; the box contains 50% of the data separated by the median, and the whiskers contain the remaining 25% at each side. TEL-AML1 leukemias expressed less miRNA-494 (P = .04) and miRNA-320a (P = .03) than other cALLs. (B) Scatterplot of the relationship of miRNA-320a (measured by Taqman) and survivin protein (measured by ELISA) among 28 cryopreserved TEL-AML1 leukemia cell samples. Two samples that were outliers were removed to “center” the remainder of the data. miRNA-320a and survivin were correlated (Spearman corrrelation: −0.38, P = .015). (C) Schematic presentation of the TEL-AML1, miRNA-494, and miRNA-320a impact upon survivin expression and cell survival. TEL-AML1 binds miRNA-494 and miRNA-320a promoters and exerts its transcriptional suppressor activity. These block miRNA-494 and miRNA-320a expression and release miRNA control of survivin expression resulting in increased resistance from apoptosis.
