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Original Article

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Blood Res 2019; 54(2):

Published online June 30, 2019

https://doi.org/10.5045/br.2019.54.2.102

© The Korean Society of Hematology

Enhanced polo-like kinase 1 expression in myelodysplastic syndromes

Kyoung Il Min1, Silvia Park1, Seung-Hwan Shin2, Yong-Rim Kwon3, Hye-Joung Kim3, Yoo Jin Kim3,4

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1Division of Hematology, Department of Internal Medicine, Seoul St. Mary’s Hematology Hospital, 2Department of Hematology, Yeoido St. Mary’s Hospital, 3Laboratory of Hematological Disease and Immunology, 4Leukemia Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Korea

Correspondence to : Yoo Jin Kim, M.D., Ph.D.
Division of Hematology, Department of Internal Medicine, Seoul St. Mary’s Hematology Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul 06591, Korea
E-mail: yoojink@catholic.ac.kr

Received: November 9, 2018; Revised: November 22, 2018; Accepted: November 25, 2018

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

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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.

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

Article

Original Article

Blood Res 2019; 54(2): 102-107

Published online June 30, 2019 https://doi.org/10.5045/br.2019.54.2.102

Copyright © The Korean Society of Hematology.

Enhanced polo-like kinase 1 expression in myelodysplastic syndromes

Kyoung Il Min1, Silvia Park1, Seung-Hwan Shin2, Yong-Rim Kwon3, Hye-Joung Kim3, Yoo Jin Kim3,4

1Division of Hematology, Department of Internal Medicine, Seoul St. Mary’s Hematology Hospital, 2Department of Hematology, Yeoido St. Mary’s Hospital, 3Laboratory of Hematological Disease and Immunology, 4Leukemia Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Korea

Correspondence to:Yoo Jin Kim, M.D., Ph.D.
Division of Hematology, Department of Internal Medicine, Seoul St. Mary’s Hematology Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul 06591, Korea
E-mail: yoojink@catholic.ac.kr

Received: November 9, 2018; Revised: November 22, 2018; Accepted: November 25, 2018

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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.

Keywords: Myelodysplastic syndromes, Polo-like kinase 1, Protein-serine-threonine kinases, DNA methylation, Gene expression

Fig 1.

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Figure 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.

Blood Research 2019; 54: 102-107https://doi.org/10.5045/br.2019.54.2.102

Fig 2.

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Figure 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.

Blood Research 2019; 54: 102-107https://doi.org/10.5045/br.2019.54.2.102

Fig 3.

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Figure 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.

Blood Research 2019; 54: 102-107https://doi.org/10.5045/br.2019.54.2.102

Fig 4.

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Figure 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.

Blood Research 2019; 54: 102-107https://doi.org/10.5045/br.2019.54.2.102

Table 1 . Baseline characteristics of patients with myelodysplastic syndrome (MDS) or secondary acute myeloid leukemia (sAML)..

Abbreviations: ANC, absolute neutrophil count; BM, bone marrow; EB, excess blasts; HMT, hypomethylating treatment; MDS, myelodysplastic syndrome; MDS-U, MDS unclassifiable; MLD, multilineage dysplasia; sAML, secondary acute myeloid leukemia; SLD, single lineage dysplasia..
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