Changes in gene expression profile due to a shift in cell population composition.

(A) The normal tissue is composed of various cell types, whereas the cancer tissue is composed predominantly of the cancerous cell type (green). Expansion of the cancer cells thus results in a decrease in the proportion of the other cell types. The overall level of expression in the cancer tissue of genes that are selectively expressed in one type of noncancer cell (yellow) would thus appear decreased (arrow), compared with that in the normal tissue, only because of the corresponding decrease in the yellow cell population. Conversely, expansion of the green cells gives rise to an apparent increase in the tissue expression level of genes specifically expressed in this cell type, regardless of whether the number of the corresponding transcripts per cell is actually increased or not. (B) Previous comparisons of transcriptomes in the studies of blood cells have been performed with MNCs of sample A and sample B, irrespective of their cellular compositions (MNC screening). In the present study, transcriptomes were compared between leukemic blasts (green) to reduce the occurrence of pseudopositive and pseudonegative results generated by a shift in cell population composition. For this approach (BAMP screening), the target leukemic blasts were purified by affinity chromatography on a column containing anti-AC133.