Suppression of chronic lymphocytic leukemia progression by CXCR4 inhibitor WZ811.

CXCR4 is a chemokine and chemokine receptor pair playing critical roles in tumorigenesis. Overexpression of C-X-C chemokine receptor type 4 (CXCR4) is a hallmark of many hematological malignancies including acute myeloid leukemia, chronic lymphocytic leukemia and non-Hodgkin's lymphoma, and generally correlates with a poor prognosis. A highly potent competitive antagonist of CXCR4, WZ811, recently has been identified with suppression of cancer cells aggressive in a variety of cancers. However, the effects of WZ811 on chronic lymphocytic leukemia cells have not yet been defined. The effect of WZ811 on chronic lymphocytic leukemia cells TF-1 and UT-7 cells in proliferation, colony formation, and cell migration in vitro were measured respectively. Decreased in cell viability, colony formation, migration, and survival with cell cycle arrest and higher sensitivity to docetaxel in vitro was observed upon WZ811 treatment. In mouse xenograft models developed with human leukemia cells, WZ811 exhibited tumor growth inhibition. Collectively, we have demonstrated that CXCR4 inhibition by WZ811 has the potential for the treatment of human hematological malignancies. This study demonstrated that WZ811 may be a novel approach in the treatment of chronic lymphocytic leukemia.