Proplatelet formation. (A) Megakaryocytes generate platelets by remodelling their cytoplasm into long, beaded extensions, called proplatelets, that function as the assembly lines of platelet production. The demarcation membrane system (DMS), an elaborate invaginated membrane network found in mature megakaryocytes, reorganizes to provide the abundant surface membrane material required for proplatelet formation. (B) IMiDs cause aromatase to become a neo-substrate of cereblon preventing endogenous estradiol synthesis and demarcation membrane formation in human megakaryocytes. Lack of demarcation membrane causes abolition of proplatelet formation.