Roadmap for developing and validating therapeutically


13-Nov-2019 08:23

The grouping of cases according to similar gene expression signatures is often referred to as clustering.

The underlying assumption is that cases with the same gene expression profiles may carry the same genetic abnormality.

Furthermore, it may enable the development and application of specific treatment modalities targeted to underlying oncogenic abnormalities.

The efficacy of such drugs as all- Despite great progress, much of the heterogeneity of AML remains to be resolved.

However, a subset of 6 patients in this cluster did not show any CEBPA mutation (green indicates CEBPA wild-type).

roadmap for developing and validating therapeutically-59

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Insight into cytogenetic and genetic aberrations is invaluable for diagnosis, and it may also allow for better understanding of the pathobiology.

In an unsupervised approach this is done in an unbiased way, ie without the use of external information such as mutations or karyotypic subtypes.

This procedure is therefore representative of class discovery.

To answer whether gene expression profiling would enable identification of potential heterogeneity within this apparently homogeneous subgroup, in panel B the 44 cases were reclustered as an isolated cohort.

For this analysis, only probe sets that showed a variable expression within these 44 AML cases were taken into account, as defined by a fold change of 3.5 to the mean in log2 scale in at least 1 case.

(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.



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