TP53RK in Multiple Myeloma: A New Therapeutic Target?
p53-related protein kinase (TP53RK) is a targetable prognostic marker for patients with multiple myeloma.
p53-related protein kinase (TP53RK) is a targetable prognostic marker for patients with multiple myeloma, according to an article published in Blood.1
A profile of genetic expression suggested that increased TP53RK expression is a causal factor of normal plasma cells progressing into myeloma cells. For this paper, the authors analyzed the gene expression profiles of myeloma cells to determine the role of TP53RK in myeloma progression, and whether TP53RK inhibition is likely to improve clinical outcomes.
Cells from patients with active disease had high TP53RK expression, suggesting that TP53RK levels predict disease progression. Patients with newly-diagnosed disease had shorter survival if tumor cells had high TP53RK expression.
Immunomodulatory agents such as pomalidomide were shown to bind to TP53RK and “inhibit its kinase activity.” This inhibition triggered myeloma cell apoptosis, though it is unclear whether this method would be effective in clinical settings.
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The authors concluded that TP53RK expression is both a prognostic marker and a therapeutic target for patients with multiple myeloma. More research is needed, however, to develop selective TP53RK inhibitors.
- Hideshima T, Cottini F, Nozawa Y, et al. p53-related protein kinase confers poor prognosis and represents a novel therapeutic target in multiple myeloma. Blood. 2017 Jan 12. 10.1182/blood-2016-09-738500 [Epub ahead of print