Global gene expression in classification, pathogenetic understanding and identification of therapeutic targets in...

Global gene expression analysis by way of DNA microarrays and real time quantitative PCR provides an important supplement to established diagnosis and classification of malignant disease. A comprehensive molecular understanding of the regulatory modules involved in carcinogenesis should also be important for improved identification of therapeutic targets and thus for future individualized therapy, e.g., by allowing therapeutic synergy when designing combination therapy against vulnerable points in the malignant cells. The therapeutic potential of knowledge obtained from global gene expression analysis of malignant cells is crucially dependent upon a similarly fine-grained knowledge of gene regulation in normal cells. The deviant gene expression patterns should therefore be assessed on a background of gene expression associated with housekeeping functions, particular differentiation stages and epiphenomena due to genomic instability. Since malignant cells originate from transformed precursor cells, such reference information can be obtained from investigations of embryonic and somatic stem cells. Much has recently been learned about the regulatory modules of normal hematopoietic stem cells and their malignant counterparts, and new biologically and clinically relevant patient subgroups as well as novel prognostic and therapeutic molecular markers have been identified. The present review weighs up the results and their potentialities with reference to gene expression analysis in acute myeloid leukemia (AML).