| Summary: | <i>Background and objectives:</i> Mutational analysis has led to a better understanding of acute myeloid leukemia (AML) biology and to an improvement in clinical management. Some of the most important mutations that affect AML biology are represented by mutations in genes related to methylation, more specifically: <i>TET2</i>, <i>IDH1</i>, <i>IDH2</i> and <i>WT1</i>. Because it has been shown in numerous studies that mutations in these genes lead to similar expression profiles and phenotypes in AML, we decided to assess if mutations in any of those genes interact with other genes important for AML. <i>Materials and Methods:</i> We downloaded the clinical data, mutational profile and expression profile from the TCGA LAML dataset via cBioPortal. Data were analyzed using classical statistical methods and functional enrichment analysis software represented by STRING and GOrilla. <i>Results:</i> The first step we took was to assess the 196 AML cases that had a mutational profile available and observe the mutations that overlapped with <i>TET2/IDH1/2/WT1</i> mutations. We observed that <i>RUNX1</i> mutations significantly overlap with <i>TET2/IDH1/2/WT1</i> mutations. Because of this, we decided to further investigate the role of <i>RUNX1</i> mutations in modulating the level of <i>RUNX1</i> mRNA and observed that <i>RUNX1</i> mutant cases presented higher levels of <i>RUNX1</i> mRNA. Because there were only 16 cases of <i>RUNX1</i> mutant samples and that mutations in this gene determined a change in mRNA expression, we further observed the correlation between <i>RUNX1</i> and other mRNAs in subgroups regarding the presence of hypermethylating mutations and <i>NPM1</i>. Here, we observed that both <i>TET2/IDH1/2/WT1</i> and <i>NPM1</i> mutations increase the number of genes negatively correlated with <i>RUNX1</i> and that these genes were significantly linked to myeloid activation. <i>Conclusions:</i> In the current study, we have shown that <i>NPM1</i> and <i>TET2/IDH1/2/WT1</i> mutations increase the number of negative correlations of <i>RUNX1</i> with other transcripts involved in myeloid differentiation.
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