cigb-300 and Leukemia--Lymphocytic--Chronic--B-Cell

Chronic lymphocytic leukemia (CLL) remains an incurable malignancy, urging for the identification of new molecular targets for therapeutic intervention. CLL cells rely on overexpression and hyperactivation of the ubiquitous serine/threonine protein kinase CK2 for their viability in vitro. CIGB-300 is a cell-permeable selective CK2 inhibitor peptide undergoing clinical trials for several cancers. Here, we show that CIGB-300 promotes activation of the tumor suppressor PTEN and abrogates PI3K-mediated downstream signaling in CLL cells. In accordance, CIGB-300 decreases the viability and proliferation of CLL cell lines, promotes apoptosis of primary leukemia cells and displays antitumor efficacy in a xenograft mouse model of human CLL. Our studies provide pre-clinical support for the testing and possible inclusion of CK2 inhibitors in the clinical arsenal against CLL.

Topics: Aged; Aged, 80 and over; Animals; Apoptosis; Casein Kinase II; Cell Growth Processes; Cell Line, Tumor; Cell Survival; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Male; Mice; Mice, Nude; Middle Aged; Peptides, Cyclic; Phosphatidylinositol 3-Kinases; Protein Kinase Inhibitors; PTEN Phosphohydrolase; Random Allocation; Signal Transduction; Xenograft Model Antitumor Assays