Casein Kinase 2 (CK2): A Possible Therapeutic Target in Acute Myeloid Leukemia

SIMPLE SUMMARY: Acute myeloid leukemia (AML) is an aggressive blood cancer disease that can only be cured by intensive anticancer treatment, and for several patients, allogeneic stem cell transplantation is needed. The protein kinase casein kinase 2 (CK2) is an intracellular signaling molecule that supports cellular growth and survival. This is true both for normal and cancer cells, and the growth- and survival-supporting effects seem to be more important for many cancer cells (including AML cells) than for normal cells. Several pharmacological inhibitors of CK2 have been developed, and this therapeutic strategy is now tried in patients with various malignant diseases. In this article, we review available studies suggesting CK2 inhibition as an effective strategy also for the treatment of AML, either as monotherapy or as a part of drug combinations. ABSTRACT: The protein kinase CK2 (also known as casein kinase 2) is one of the main contributors to the human phosphoproteome. It is regarded as a possible therapeutic strategy in several malignant diseases, including acute myeloid leukemia (AML), which is an aggressive bone marrow malignancy. CK2 is an important regulator of intracellular signaling in AML cells, especially PI3K–Akt, Jak–Stat, NFκB, Wnt, and DNA repair signaling. High CK2 levels in AML cells at the first time of diagnosis are associated with decreased survival (i.e., increased risk of chemoresistant leukemia relapse) for patients receiving intensive and potentially curative antileukemic therapy. However, it is not known whether these high CK2 levels can be used as an independent prognostic biomarker because this has not been investigated in multivariate analyses. Several CK2 inhibitors have been developed, but CX-4945/silmitasertib is best characterized. This drug has antiproliferative and proapoptotic effects in primary human AML cells. The preliminary results from studies of silmitasertib in the treatment of other malignancies suggest that gastrointestinal and bone marrow toxicities are relatively common. However, clinical AML studies are not available. Taken together, the available experimental and clinical evidence suggests that the possible use of CK2 inhibition in the treatment of AML should be further investigated.