Blood: Aromatase is a new substrate of cereblon, involved in IMiDs induced platelet reduction

Immunomodulation drugs (IMiDs) are key drugs for the treatment of chromosomal 5q deficiency multiple myeloma and myeloma hyperplasia syndromeIMiD plays its multi-effect by raising new substrates to E3 connecting enzymececereblon, i.eacting as a substrate receptor for the E3 ubiquitin nephrotic enzyme complex;in clinical practice, IMiDs can induce platelet reduction, which often leads to the discontinuation of IMiDs treatmentIn this study, the researchers aimed to analyze the molecular mechanisms of platelet reduction induced by IMiDs therapyresearchers have found that IMiD severely affects platelet formation by inhibiting the transmission of self-secreted estradiol signals in human giant nuclear cells, a key step in functional platelet productionIn addition, the researchers identified aromatase, an enzyme indispensable in estradiol biosynthesis, as a new type of substrate for cereblonIMiDs promote the collection of aromatase to cereblon, causing aromatase to degrade by protease-dependent methodsFinally, in the bone marrow of patients with multiple myeloma that was treated with IMiDs that led to platelet reduction, the aromatase significantly degradedthis study shows that aromatase is a new type of substrate of cereblon, involved in IMiDs-induced platelet reduction