Journal
LEUKEMIA RESEARCH
Volume 39, Issue 4, Pages 462-470Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.leukres.2015.01.007
Keywords
AML; PLK1 inhibition; BI2536; BI6727; Volasertib; Bone marrow biopsy; Live cell imaging; Hematopoietic cells
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Funding
- Forschungskommission (University Medical Center Freiburg) [MUN829/11]
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Polo-like kinase 1 (PLK1) is an important regulator of the cell cycle and is overexpressed in various solid and hematological malignancies. Small molecule inhibitors targeting PLK1, such as BI2536 or BI6727 (Volasertib) are a promising therapeutic approach in such malignancies. Here, we show a loss of specifically localized PLK1 in AML blasts in vivo, accompanied by mitotic arrest with transition into apoptosis, in bone marrow biopsies of AML patients after treatment with BI2536. We verify these results in live cell imaging experiments with the AML cell line HL-60, and demonstrate that non-neoplastic, immortalized lymphoblastoid cells are also sensitive to PLK1 inhibition. It is demonstrated that normal granulopoietic precursors have similar PLK1 expression levels as leukemic blasts. These results are in line with the adverse effects of PLK1 inhibition and underline the great potential of PLK1 inhibitors in the treatment of AML. (C) 2015 Elsevier Ltd. All rights reserved.
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