They hypothesized that the mechanisms through which the mutant SETBP1 protein exerts its oncogenic activity may be more complicated, and could involve an aberrant hypomethylation of the SETBP1 promoter or alterations of upstream regulators such as MECOM [58, 61, 62] or of miRNAs such as MIR_4319, an intronic miRNA that was found to be downregulated in a case of PMF evolving to AML and expressing higher levels of SETBP1 mRNA [23]. Here, SETBP1 is linked to acute myeloid leukemia.