IFNα activates the JAK/STAT pathway, which leads to the translocation of STAT1/2 and IRF-9 to the nucleus that induces the p53 gene expression through the IFN-sensitive response element (ISRE) in its promoter. In parallel, at the level of JAK2V617F-positive stem or progenitor cells, the thrombopoietin (TPO) receptor activates downstream signaling pathways, especially the PI3K/AKT/mammalian target of rapamycin (mTOR) pathway. In turn, the translation of the ribonucleoprotein LA increases, resulting in enhancement of MDM2 translation and the degradation of p53 tumor suppressor. The use of RG7112, an antagonist of MDM2, alleviates the p53 degradation and strongly contributes to increase the levels of p53 protein stimulated by INFα, triggering cell death and cell cycle arrest.