Back to Search
Start Over
Therapeutic polo-like kinase 1 inhibition results in mitotic arrest and subsequent cell death of blasts in the bone marrow of AML patients and has similar effects in non-neoplastic cell lines.
- Source :
-
Leukemia research [Leuk Res] 2015 Apr; Vol. 39 (4), pp. 462-70. Date of Electronic Publication: 2015 Jan 28. - Publication Year :
- 2015
-
Abstract
- 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.<br /> (Copyright © 2015 Elsevier Ltd. All rights reserved.)
- Subjects :
- Aged
Aged, 80 and over
Antimitotic Agents pharmacology
Blast Crisis drug therapy
Blast Crisis enzymology
Blast Crisis pathology
Blotting, Western
Bone Marrow enzymology
Bone Marrow pathology
Cell Cycle Proteins metabolism
Cell Proliferation drug effects
Female
Humans
Immunoenzyme Techniques
Leukemia, Myeloid, Acute enzymology
Male
Protein Serine-Threonine Kinases metabolism
Proto-Oncogene Proteins metabolism
RNA, Messenger genetics
Real-Time Polymerase Chain Reaction
Reverse Transcriptase Polymerase Chain Reaction
Tumor Cells, Cultured
Polo-Like Kinase 1
Apoptosis drug effects
Bone Marrow drug effects
Cell Cycle Proteins antagonists & inhibitors
Leukemia, Myeloid, Acute drug therapy
Leukemia, Myeloid, Acute pathology
Mitosis drug effects
Protein Serine-Threonine Kinases antagonists & inhibitors
Proto-Oncogene Proteins antagonists & inhibitors
Pteridines pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1873-5835
- Volume :
- 39
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Leukemia research
- Publication Type :
- Academic Journal
- Accession number :
- 25697066
- Full Text :
- https://doi.org/10.1016/j.leukres.2015.01.007