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Updated: Jun 1, 2026
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Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs
Published on: May 15, 2019
Activation of coagulation by a thalidomide-based regimen.
Asuka Hoshi1, Aya Matsumoto, Jihwa Chung
1Laboratory Molecular Genetics of Hematology, Graduate School of Healthcare Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, Japan.
Summary
Thalidomide (Thal) combined with chemotherapy or dexamethasone may increase deep vein thrombosis (DVT) risk by promoting procoagulant activity. This occurs through phosphatidylserine exposure or tissue factor expression, suggesting a need for anticoagulant strategies.
Area of Science:
- Hematology
- Oncology
- Pharmacology
Background:
- Thalidomide (Thal) combined with chemotherapy or steroids improves multiple myeloma response rates.
- Deep vein thrombosis (DVT) is a serious side effect of Thal-based regimens, but its mechanism remains unclear.
Purpose of the Study:
- To investigate the in vitro procoagulant effects of Thal in combination with chemotherapeutic agents.
- To elucidate the role of tissue factor (TF) and phosphatidylserine in Thal-induced DVT.
Main Methods:
- Utilized human vascular endothelial (EAhy926), monocytic (THP-1), and myeloma (RPMI8226) cell lines.
- Examined the effects of doxorubicin hydrochloride (Dox), dexamethasone (Dex), and Thal, alone and in combination, on TF expression and phosphatidylserine exposure.
- Assessed procoagulant activity (PCA) induction.
Main Results:
- Dexamethasone (Dex) increased TF expression and PCA in endothelial and monocytic cells.
- Doxorubicin (Dox) and Thal-Dox significantly increased phosphatidylserine exposure and PCA in THP-1 cells.
- Thalidomide (Thal) alone showed modest increases in phosphatidylserine exposure.
Conclusions:
- Thal-based regimens may induce endothelial cell and monocyte PCA via phosphatidylserine exposure or TF expression.
- Thal's antiangiogenic activity might prolong this induction.
- Prophylactic anticoagulant strategies are recommended for Thal-based combination therapies.
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