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How Pomalidomide Works to Kill Multiple Myeloma
How Pomalidomide Works to Kill Multiple Myeloma
Posted Apr 06, 2021

The immunomodulators (thalidomide, lenalidomide and pomalidomide) are a staple class of drugs regularly used in myeloma care. Pomalidomide is often used once patients become resistant to lenalidomide (Revlimid), but how it actually works to kill myeloma has been unclear. Tokyo Institute of Technology, Tokyo Medical University and Saitama Medical University researchers recently published insights into how pomalidomide fights myeloma in Nature Chemical Biology

Lenalidomide is known to affect the cereblon pathway, but the Japanese researchers noticed that lenalidomide and pomalidomide affected another protein differently. Lenalidomide caused a small breakdown of a protein called ARID2 and some reductions in the MYC gene, whereas pomalidomide had stronger effects on both. 

The ARID2 protein is a member of the ARID family of DNA-binding proteins. This family of proteins have a role in fetal pattern development, cell lineage gene regulation, cell cycle control, transcriptional regulation and chromatin structure changes. 


The researchers showed that pomalidomide causes the breakdown of a protein called ARID2. ARID2 is involved in the regulation of pomalidomide target genes including MYC. MYC is a well known "master regulator of cell growth in myeloma" (learn more about MYC here and here). Cells that had lower levels of ARID2 after being treated with pomalidomide also had lower levels of MYC. 

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