NFE2L2 and myelofibrosis: Third, taking into account that Nrf2 functions as a negative regulator of cell-cycle entry in HSCs, maintaining the delicate balance between HSC quiescence and self-renewal [11] and Nrf2 also has a key role in governing the retention of HSCs and their homing to the bone marrow niche [11], Nrf2 deficiency in MPNs may likely contribute to the egress of CD34+ cells from bone marrow niches to seed preferentially in the spleen and liver (myelofibrosis with myeloid metaplasia).