Inhibition of Syk protein tyrosine kinase induces apoptosis and blocks proliferation in T-cell non-Hodgkin's lymphoma cell lines

Spleen tyrosine kinase (Syk) is a potent target for GvHD prevention at different cellular levels

“…Recent data indicate that T-cell non-Hodgkin's lymphoma cell proliferation is dependent on Syk, 44 and that many of the same signaling pathways that are active in malignant lymphoma cells where Syk inhibitors are already applied clinically 45 are also relevant for the activation of non-malignant lymphocytes. To address the mechanism for the potent protective in vivo effects against Tc-mediated GvHD, we first turned toward Tcs and observed reduced proliferative allo-responses in vitro that were consistent with the reduced expansion of Tc luc documented in vivo.…”

“…On the basis of the antineoplastic effects of Fostamatinib in non-Hodgkin lymphomas, 44,45 Syk inhibition may even be synergistic with allo responses and render leukemias more susceptible to Tc-mediated cytotoxicity.…”

New molecular insights into peripheral T cell lymphomas

“…In a subset of PTCL-NOSs, Streubel et al detected the t(5;9)(q33; q22) translocation, which leads to the fusion transcript ITK-SYK with constitutive kinase activity (61) and possible pathogenic significance. Indeed, inhibition of SYK, a TCR downstream molecule, was found to be effective ex vivo by inhibiting cell proliferation and inducing cell death (62). More recently, somatic mutations of isocitrate dehydrogenase 2 (IDH2) have been specifically detected in AITL (63), but their role has not yet been established.…”

Evolving therapy of peripheral T-cell lymphoma: 2010 and beyond

“…The recent finding of SYN/ITK translocations in PTCL tissues has suggested that syk protein tyrosine kinase inhibitors may be active in the clinic. While T-cell non-Hodgkin's lymphoma cell lines were sensitive in vitro, early clinical trial data have not been promising [Wilcox et al 2010]. Similarly, PI3K pathways have been shown to be activated in aggressive T-cell lymphomas, and clinical trials with agents inhibiting this pathway are underway [Martin-Sanchez et al 2010].…”