TPO and myelofibrosis: In mice, TPO overexpression leads to the development of myelofibrosis, which correlates with an increase in MK numbers.77 Similarly, GATA1 deficiency results in elevated immature MK levels and severe myelofibrosis.78 An increase in MK numbers in patients with myelofibrosis has been linked to higher IL-13 levels79 and widespread mutations in the calreticulin gene, which impair calcium release from the endoplasmic reticulum.80 However, the exact mechanism of increased MKs contributing to MPN pathogenesis remains unclear.