SHH and myelofibrosis: Starting with the evidence that IGFBP-6 levels are significantly increased in PMF patients with wild-type Janus Kinase 2, our recent study demonstrated a new role of the axis IGFBP-6/SHH/Toll-like receptor 4 as involved in alterations of the primary myelofibrosis microenvironment and that IGFBP-6 may play a fundamental role in activating SHH pathway during the fibrotic process [58].