CDK8 and myeloproliferative disorder: As in CRC, CDK8 and its paralog CDK19 restrain the increased activation of key super-enhancer-associated genes, affecting global gene expression in acute myeloid leukemia (AML) cells that depend on precise super-enhancer-associated gene expression, and CDK8 inhibition has shown potent effects.371 In myeloproliferative neoplasms and JAK-mutated AML, CDK8 phosphorylates STAT1, leading to constitutive activation of its transcriptional program.