Roadmap for developing and validating therapeutically
Five of the 16 clusters have been labeled as clusters 4, 5, 9, 12, and 13.
One finding of the original study was the tight aggregation into distinct clusters of AML cases with cytogenetic abnormalities that predict good risk.
Support for this hypothesis has come from observations, now confirmed by several research groups, that particular cytogenetic AML subtypes (eg, AMLs with t(8;21), t(15;17), and inv(16)) each share distinctive GEP profiles (Figure 1A).
Summary of GEP findings in a cohort of 285 cases of AML.
In particular, genome-wide gene expression profiling (GEP) using DNA microarrays has been extensively used for improved understanding of the diagnosis, prognosis, and pathobiology of this heterogeneous disease.(A) A previous study of 285 cases of AML revealed 16 subgroups (clusters) of cases based on similarities in gene expression profiles.22 Pairwise correlations between these AML cases are shown on the left.The cells in the visualization are colored by Pearson correlation coefficient values, with deeper colors depicting higher positive (red) or negative (blue) correlations, as indicated by the scale bar.Now, some 10 years later, we shall discuss the results of a decade of experience with GEP as regards diagnosis, prognosis and biology of AML in the context of clinical studies. And is it possible to extract new insights into the pathobiology of AML from clinical GEP data?Is it possible to identify new clinically relevant subgroups of AML using GEP? A straightforward way of using GEP is to compare expression profiles between cases of AML and to search for similarities and differences.
NPM1 mutational status is depicted next to each case (red indicates NPM1 mutant; green, NPM1 wild-type).24 The figure illustrates that NPM1 mutations were not randomly distributed over the 16 previously defined clusters, but enriched in several of them.