The main resistance mechanisms are activation of certain pathways, such as Cyclin E-CDK2 or phosphoinositide 3-kinase (PI3K)/serine-threonine protein kinase (AKT)/mammalian target of rapamycin (mTOR) pathway activation, downregulation of pRP or phosphatase and tensin homolog (PTEN) and finally ET resistance [62,63,64]. The gene discussed is CDK2; the disease is essential thrombocythemia.