Applications of microarray technology to Acute Myelogenous Leukemia

Abstract

Microarray technology is a powerful tool, which has been applied to further the understanding of gene expression changes in disease. Array technology has been applied to the diagnosis and prognosis of Acute Myelogenous Leukemia (AML). Arrays have also been used extensively in elucidating the mechanism of and predicting therapeutic response in AML, as well as to further define the mechanism of AML pathogenesis. In this review, we discuss the major paradigms of gene expression array analysis, and provide insights into the use of software tools to annotate the array dataset and elucidate deregulated pathways and gene interaction networks. We present the application of gene expression array technology to questions in acute myelogenous leukemia; specifically, disease diagnosis, treatment and prognosis, and disease pathogenesis. Finally, we discuss several new and emerging array technologies, and how they can be further utilized to improve our understanding of AML.

Keywords: acute myelogenous leukemia; diagnostics; downstream genetic targets; gene expression profiling; prognosis; therapeutics.

Figure 1. Oligonucleotide microarrays

A) cDNA synthesis, labeling and hybridization to oligonucleotide array slides. B) Correlation coefficient analysis of gene expression data, showing, in red, probes with fluorescent intensities above the threshold of detection, and in yellow, absent fluorescence. C) Scatter plot analysis of gene expression data, showing the correlation between two of the samples that clustered together, where most probes have similar expression levels, with some probes differentially expressed between these samples. D) Hierarchical clustering of microarray data; in this analysis, samples with similar gene expression profiles are grouped together, cluster of genes is shown on the Y-axis and dendogram or cluster of samples is seen in the X-axis.

Figure 2

A ChIP-on-Chip workflow. Each step of the chromatin immunoprecipitation stage is optimized for every cell and tissue type. Enrichment analysis to determine successful immunoprecipitation is performed using quantitative real time PCR using primers against target DNA sequences known to be bound by the protein of interest. Large scale genome binding analyses are dependent on the array platform used in the study—these can include promoter arrays, whole genome tiling arrays, or custom made targeted tiling arrays.