Blood Res.  2019 Jun;54(2):102-107. 10.5045/br.2019.54.2.102.

Enhanced polo-like kinase 1 expression in myelodysplastic syndromes

Affiliations
  • 1Division of Hematology, Department of Internal Medicine, Seoul St. Mary's Hematology Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
  • 2Department of Hematology, Yeoido St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
  • 3Laboratory of Hematological Disease and Immunology, College of Medicine, The Catholic University of Korea, Seoul, Korea. yoojink@catholic.ac.kr
  • 4Leukemia Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Korea.

Abstract

BACKGROUND
Cancer is characterized by uncontrolled cellular proliferation, and Polo-like kinase 1 (PLK1), a key regulator of the cell cycle, is overexpressed in many cancers, including acute leukemia and lymphoma. However, the dynamics of PLK1 transcription in myelodysplastic syndromes (MDS) are unknown. This study aimed to investigate the transcript dynamics of PLK1 and determine its role in the pathophysiology of MDS.
METHODS
PLK1 mRNA obtained from the bone marrow samples of 67 patients with MDS, 16 patients with secondary acute myeloid leukemia (sAML), and 10 healthy controls were analyzed using quantitative real-time PCR and compared according to various clinical parameters.
RESULTS
The median PLK1 expression levels differed slightly, but not significantly, between MDS and sAML patients [661.21 (range, 29.38-8,987.31) vs. 1,462.05 (32.22-5,734.09), respectively], but were significantly higher (P<0.001) than the levels in the healthy controls [19.0 (1.60-49.90)]. Further analyses of PLK1 levels according to the WHO classification of MDS, prognostic risk groups, karyotype risk groups, marrow blast percentage, and depth of cytopenia did not reveal any significant associations. In patients progressing to sAML, PLK1 expression levels differed significantly according to the presence or absence of resistance to hypomethylation treatment (2,470.58 vs. 415.98, P=0.03).
CONCLUSION
PLK1 is upregulated in MDS patients; however, its role in the pathophysiology of MDS is unclear. Gene upregulation in cases with pharmacotherapeutic resistance warrants further investigation.

Keyword

Myelodysplastic syndromes; Polo-like kinase 1; Protein-serine-threonine kinases; DNA methylation; Gene expression

MeSH Terms

Bone Marrow
Cell Cycle
Cell Proliferation
Classification
DNA Methylation
Gene Expression
Humans
Karyotype
Leukemia
Leukemia, Myeloid, Acute
Lymphoma
Myelodysplastic Syndromes*
Phosphotransferases*
Protein-Serine-Threonine Kinases
Real-Time Polymerase Chain Reaction
RNA, Messenger
Up-Regulation
Phosphotransferases
Protein-Serine-Threonine Kinases
RNA, Messenger

Figure

  • Fig. 1 PLK1 expression levels in healthy controls and patients with MDS and sAML. Abbreviations: 18S rRNA, 18S ribosomal RNA; MDS, myelodysplastic syndromes; PLK1, polo-like kinase 1 gene; sAML, secondary acute myeloid leukemia.

  • Fig. 2 PLK1 expression levels in MDS patients according to WHO classification (A) and IPSS-R (B). Abbreviations: 18S rRNA, 18S ribosomal RNA; Int, intermediate; IPSS-R, Revised International Prognostic Scoring System; PLK1, polo-like kinase 1 gene; MDS, myelodysplastic syndromes; MDS-EB-1, MDS with excess blast 1; MDS-EB-2, MDS with excess blast 2; MDS-SLD, MDS with single lineage dysplasia; MDS-MLD, MDS with multilineage dysplasia; MDS-U, MDS unclassifiable; WHO, World Health Organization.

  • Fig. 3 PLK1 expression levels in MDS patients according to prognostic factors: Bone marrow blast percentage (A), IPSS-R cytogenetic categories (B), absolute neutrophil count (C), hemoglobin level (D), and platelet count (E). Abbreviations: 18S rRNA, 18S ribosomal RNA; ANC, absolute neutrophil count; Int, intermediate; IPSS-R, Revised International Prognostic Scoring System; MDS, myelodysplastic syndromes; PLK1, polo-like kinase 1 gene; sAML, secondary acute myeloid leukemia.

  • Fig. 4 PLK1 expression levels in patients with sAML according to whether the disease developed “naturally” or after hypomethylating treatment failure. Abbreviations: 18S rRNA, 18S ribosomal RNA; PLK1, polo-like kinase 1 gene; sAML, secondary acute myeloid leukemia; sAML-HF, patients who developed secondary acute myeloid leukemia after hypomethylating treatment failure; sAML-natural, patients who developed secondary acute myeloid leukemia with no prior disease-modifying treatment.


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