For the first time, it is shown that NFATC1—a transcription factor that is induced upon inflammatory stimuli—converts FLT3ITD-induced myeloproliferation into an FLT3ITD inhibitor-resistant, lethal AML, which is associated with NFATC1-dependent de novo recruitment of key oncogenic signaling pathways. This evidence concerns the gene NFATC1 and acute myeloid leukemia.