Targeting the Spleen Tyrosine Kinase with Fostamatinib as a Strategy against Waldenstrom Macroglobulinemia.

ABSTRACT:

Purpose

Waldenström macroglobulinemia (WMG) is a lymphoproliferative disorder characterized by good initial responses to standard therapeutics, but only a minority of patients achieve complete remissions, and most inevitably relapse, indicating a need for novel agents. B-cell receptor signaling has been linked to clonal evolution in WMG, and Spleen tyrosine kinase (Syk) is overexpressed in primary cells, suggesting that it could be a novel and rational target.

Experimental design

We studied the impact of the Syk inhibitor fostamatinib on BCWM.1 and MWCL-1 WMG-derived cell lines both in vitro and in vivo, as well as on primary patient cells.

Results

In WMG-derived cell lines, fostamatinib induced a time- and dose-dependent reduction in viability, associated with activa

SUBMITTER: Kuiatse I 

PROVIDER: S-EPMC4737551 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature