Roadmap for developing and validating therapeutically Chat sexy arabic online
The past decade has shown a marked increase in the use of high-throughput assays in clinical research into human cancer, including acute myeloid leukemia (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.
However, a subset of 6 patients in this cluster did not show any CEBPA mutation (green indicates CEBPA wild-type).
It was found that these cases differed in their CEBPA m RNA expression as compared with the CEBPA mutant AMLs, as indicated by the histograms depicting signal intensity values for the CEBPA probe set on the microarray.
(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.
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).
Insight into cytogenetic and genetic aberrations is invaluable for diagnosis, and it may also allow for better understanding of the pathobiology.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.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.Cluster 4 was found to associate with CEBPA mutations (red indicates CEBPA mutant).
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In addition, NOTCH1 mutations were found as common characteristics of this subgroup (red indicates NOTCH1 mutation; green, NOTCH1 wild-type).31 (B) In the original analysis of 285 AML cases (panel A left), the 44 cases in cluster 5 aggregated very tightly, as indicated by the deep red colors representing positive Pearson correlation coefficients.