CK1δ in lymphoma: gene expression and mutation analyses and validation of CK1δ kinase activity for therapeutic application.
The prognosis of lymphoid neoplasms has improved considerably during the last decades. However, treatment response for some lymphoid neoplasms is still poor, indicating the need for new therapeutic approaches. One promising new strategy is the inhibition of kinases regulating key signal transduction pathways, which are of central importance in tumorigenesis. Kinases of the CK1 family may represent an attractive drug target since CK1 expression and/or activity are associated with the pathogenesis of malignant diseases. Over the last years efforts were taken to develop highly potent and selective CK1-specific inhibitor compounds and their therapeutic potential has now to be proved in pre-clinical trials. Therefore, we analyzed expression and mutational status of CK1δ in several cell lines representing established lymphoma entities, and also measured the mRNA expression level in primary lymphoma tissue as well as in non-neoplastic blood cells. For a selection of lymphoma cell lines we furthermore determined CK1δ kinase activity and demonstrated therapeutic potential of CK1-specific inhibitors as a putative therapeutic option in the treatment of lymphoid neoplasms.
Department of Pathology, Ulm University Hospital Ulm, Germany.
B Sophia
BS
Winkler
Department of General and Visceral Surgery, Surgery Center, Ulm University Hospital Ulm, Germany.
Franziska
F
Oltmer
Department of General and Visceral Surgery, Surgery Center, Ulm University Hospital Ulm, Germany.
Julia
J
Richter
Department of General and Visceral Surgery, Surgery Center, Ulm University Hospital Ulm, Germany.
Joachim
J
Bischof
Department of General and Visceral Surgery, Surgery Center, Ulm University Hospital Ulm, Germany.
Pengfei
P
Xu
Department of Neurosurgery, Ulm University Hospital Ulm, Germany.
Timo
T
Burster
Department of Pathology, Ulm University Hospital Ulm, Germany.
Frank
F
Leithäuser
Department of General and Visceral Surgery, Surgery Center, Ulm University Hospital Ulm, Germany.
Uwe
U
Knippschild
CK1; cell cycle; inhibitor; lymphoma; mutation analysis; therapy