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SYK-dependent tonic B-cell receptor signaling is a rational treatment target in diffuse large B-cell lymphoma
| Content Provider | Scilit |
|---|---|
| Author | Chen, Linfeng Monti, Stefano Juszczynski, Przemyslaw Daley, John Chen, Wen Witzig, Thomas E. Habermann, Thomas M. Kutok, Jeffery L. Shipp, Margaret A. |
| Copyright Year | 2008 |
| Description | The role of B-cell receptor (BCR)–mediated survival signals in diffuse large B-cell lymphoma (DLBCL) remains undefined. Ligand-induced BCR signaling induces receptor oligomerization, Igα/β immunoreceptor tyrosine-based activation motif (ITAM) phosphorylation, and activation of the spleen tyrosine kinase (SYK), which initiates downstream events and amplifies the initial BCR signal. BCRs also transmit low-level tonic survival signals in the absence of receptor engagement. Herein, we assess the role of SYK-dependent tonic BCR survival signals in DLBCL cell lines and primary tumors and evaluate the efficacy of an ATP-competitive inhibitor of SYK, R406, in vitro. R406 induced apoptosis of the majority of examined DLBCL cell lines. In R406-sensitive DLBCL cell lines, R406 specifically inhibited both tonic- and ligand-induced BCR signaling (autophosphorylation of SYK525/526 and SYK-dependent phosphorylation of the B-cell linker protein [BLNK]). The majority of examined primary DLBCLs also exhibited tonic- and ligand-induced BCR signaling; in these primary tumors, BCR signaling was also inhibited by R406. Of note, BCR-dependent and R406-sensitive DLBCL cell lines were independently identified as “BCR-type” tumors by transcriptional profiling. Therefore, SYK-dependent tonic BCR signaling is an important and potentially targetable survival pathway in some, but not all, DLBCLs. In addition, R406-sensitive DLBCLs can be identified by their transcriptional profiles. |
| Related Links | http://www.bloodjournal.org/content/bloodjournal/111/4/2230.full.pdf |
| Ending Page | 2237 |
| Page Count | 8 |
| Starting Page | 2230 |
| DOI | 10.1182/blood-2007-07-100115 |
| Journal | Blood |
| Issue Number | 4 |
| Volume Number | 111 |
| Language | English |
| Publisher | American Society of Hematology |
| Publisher Date | 2008-02-15 |
| Access Restriction | Open |
| Subject Keyword | Hematology Research and Experimental Medicine Survival Phosphorylation Bcr Signaling Primary Tumors Dependent Tonic Bcr Syk Apoptosis Journal: Blood (Vol- 78, Issue- 4) |
| Content Type | Text |
| Resource Type | Article |
