JAK2 and myeloproliferative disorder: From our observations, therefore, we postulate that impaired MPL expression in the MPN results in an inappropriately high plasma THPO level through failure of THPO clearance by MPN platelets and megakaryocytes, which augments activated JAK2 signaling in HPC, while weakening the ability of HSC to remain in the marrow osteoblastic niche (Fig 8).