Abstract
Many cell signaling pathways are activated or deactivated by protein tyrosine phosphorylation and dephosphorylation, catalyzed by protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs), respectively. Even though PTPs are as important as PTKs in this process, their role has been neglected for a long time. Multiple myeloma (MM) is a cancer of plasma cells, which is characterized by production of monoclonal immunoglobulin, anemia and destruction of bone. MM is still incurable with high relapse frequency after treatment. In this review, we highlight the PTPs that were previously described in MM or have a role that can be relevant in a myeloma context. Our purpose is to show that despite the importance of PTPs in MM pathogenesis, many unanswered questions in this field need to be addressed. This might help to detect novel treatment strategies for MM patients.
Highlights
The roles of protein tyrosine kinases (PTKs) in oncogenic processes have been extensively investigated during the last decades
As indicated in this figure, most of the phosphatases we reported here were described in the context of 3 crucial pathways: Janus kinase (JAK)/STAT, phosphoinositide 3-kinase (PI3K) and mitogenactivated protein kinase (MAPK) pathway
DUSP1, DUSP5 and PTP4A3 are the top three protein tyrosine phosphatases (PTPs) with the highest transcripts per million (TPM) value compared to the other PTPs in MM
Summary
The roles of protein tyrosine kinases (PTKs) in oncogenic processes have been extensively investigated during the last decades. Interest ingly, their counterparts, the protein tyrosine phosphatases (PTPs), have largely been neglected for a long time This might be due to the false notion that PTPs were enzymes whose function was only to counteract PTKs in a linear manner from receptor to target genes. Introduction of proteasome inhibitors, immuno-modulators (IMiDs), and monoclonal antibodies against cluster of differentiation (CD) (a glycoprotein on the surface of myeloma cells) have resulted in significant improvements in survival for patients with MM. Despite these advances in treatment in recent years, MM is still considered a fatal disease. The aim of this review is to emphasize that despite the importance of PTPs in MM pathogenesis, their role has not been well investigated
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