Use of macroarray technology to study the effects of DNA-binding drugs on gene expression profile of erythroid-induced human leukemic K562 cells

In this paper, we review recent data obtained in our laboratory, aimed to determine the effects of DNA-binding molecules on gene expression profile and their ability to induce differentiation in K562 cells and HbF production in erythroid precursor cells isolated from the peripheral blood of normal donors as well as thalassemia patients. Here, we focused the attention on the molecular effects of tallimustine, a DNA binding drug with selectivity for AT sequences that was demonstrated to induce erythroid differentiation of human K562 leukemia cells as well as HbF production in erythroid precursor cells. By using macroarray technology, we identified up- and down-regulated genes following treatment of K562 cells with tallimustine. These results were confirmed by reverse-transcription polymerase-chain reaction (RT-PCR) analysis. Molecular analysis of the promoter of these genes, of the sequences of the mRNA(s), of the structure of the encoded protein will allow to design decoy ODN, antisense DNA or RNA, peptides or monoclonal antibodies expected to mimick the biological effects of the employed inducer, limiting at the same time possible side effect.