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Janus kinase (JAK) proteins promote survival and proliferation of cells by activation of the STAT signaling pathway and are induced by hematopoietic cytokine and growth factor receptor activation. Constitutive activation of JAKs is seen in most patients with MPN and JAK inhibitors, such as ruxolitinib, filgotinib, and tofacitinib, have shown clinical activity in these patients.