Abstract
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.
Highlights
Lymphoid neoplasms are heterogeneous malignancies of the hematopoietic and lymphoid tissues (Jaffe et al, 2001; Harris et al, 2008)
Hodgkin lymphoma is of B cell origin with only very few exceptions, its distinct histology, immunophenotype, and clinical presentation justify separating it from other mature B cell neoplasms (Jaffe et al, 2001; Schmitz et al, 2009)
Both PMBL cell lines, MedB-1 and KARPAS-1066P, showed about twofold higher amounts of CK1δ mRNA than the other lymphoma cell lines included in our study (Figure 1A)
Summary
Lymphoid neoplasms are heterogeneous malignancies of the hematopoietic and lymphoid tissues (Jaffe et al, 2001; Harris et al, 2008). According to the current WHO classification lymphoid neoplasms are divided into Hodgkin-(HL) and Non-HodgkinLymphomas (NHL) (Jaffe et al, 2001; Harris et al, 2008). Hodgkin lymphoma is of B cell origin with only very few exceptions, its distinct histology, immunophenotype, and clinical presentation justify separating it from other mature B cell neoplasms (Jaffe et al, 2001; Schmitz et al, 2009). Mature NHL are broadly divided into B and T cell neoplasms and further sub-classified into a large number of distinct entities, according to phenotype, genotype and clinical properties. B and T lymphoblastic lymphomas are primarily pediatric, immature tumors belonging to the group of precursor lymphoid neoplasms (Borowitz and Chan, 2008)
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