TPO and Thrombocytopenia: Increased TPO levels with JAK inhibition have been observed in genetically modified mice and explained by failure to internalize and degrade TPO.29 The results in mice suggested thrombocytopenia associated with JAK inhibitors reflects JAK2 inhibition in stem cells rather than in megakaryocytes.29 Accordingly, it is possible ibrutinib somehow protects stem cells from ruxolitinib in CLL patients.