An integrated genomic analysis combining DNA sequencing, RNA-sequencing, and a methylation profiling microarray revealed that selection of co-occurring mutations in hematopoietic transcription factor genes (RUNX1/CEBPA) or RAS-RTK (receptor tyrosine kinase) pathway genes were the main drivers of acquired resistance to IDH inhibitors, suggesting that novel strategies targeting certain high-risk co-occurring mutations might improve the therapeutic efficacy of IDH inhibitors in AML [46]. This evidence concerns the gene IDH2 and acute myeloid leukemia.