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Polo-like kinase 1 is overexpressed in acute myeloid leukemia and its inhibition preferentially targets the proliferation of leukemic cells.
- Source :
-
Blood [Blood] 2009 Jul 16; Vol. 114 (3), pp. 659-62. Date of Electronic Publication: 2009 May 20. - Publication Year :
- 2009
-
Abstract
- Polo-like kinase 1 (Plk1) is a major mitotic regulator overexpressed in many solid tumors. Its role in hematopoietic malignancies is still poorly characterized. In this study, we demonstrate that Plk1 is highly expressed in leukemic cell lines, and overexpressed in a majority of samples from patients with acute myeloid leukemia compared with normal progenitors. A pharmacologic inhibitor, BI2536, blocks proliferation in established cell lines, and dramatically inhibits the clonogenic potential of leukemic cells from patients. Plk1 knockdown by small interfering RNA also blocked proliferation of leukemic cell lines and the clonogenic potential of primary cells from patients. Interestingly, normal primary hematopoietic progenitors are less sensitive to Plk1 inhibition than leukemic cells, whose proliferation is dramatically decreased by the inhibitor. These results highlight Plk1 as a potentially interesting therapeutic target for the treatment of acute myeloid leukemia.
- Subjects :
- Cell Cycle Proteins analysis
Gene Expression Regulation, Leukemic
Humans
Neoplasm Proteins
Protein Kinase Inhibitors pharmacology
Protein Serine-Threonine Kinases analysis
Proto-Oncogene Proteins analysis
Pteridines pharmacology
RNA, Small Interfering pharmacology
Tumor Cells, Cultured
Polo-Like Kinase 1
Cell Cycle Proteins antagonists & inhibitors
Cell Proliferation drug effects
Leukemia, Myeloid, Acute genetics
Leukemia, Myeloid, Acute pathology
Protein Serine-Threonine Kinases antagonists & inhibitors
Proto-Oncogene Proteins antagonists & inhibitors
Subjects
Details
- Language :
- English
- ISSN :
- 1528-0020
- Volume :
- 114
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Blood
- Publication Type :
- Academic Journal
- Accession number :
- 19458358
- Full Text :
- https://doi.org/10.1182/blood-2008-12-195867