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
Myelodysplastic syndromes (MDS) are a group of clonal hematological neoplasms characterized by ineffective dysplastic hematopoiesis, peripheral-blood cytopenia, and a high risk of progression to acute myeloid leukemia (AML) . Treatment outcomes differ among MDS patients, with median survival ranging from 6 months to 5 years . For optimal guidance in clinical decisions, various prognostic scoring systems have been developed, such as the International Prognostic Scoring System (IPSS), Revised International Prognostic Scoring System (IPSS-R), and World Health Organization Classification-Based Prognosis Scoring System (WPSS) . According to these scoring systems, extent of cytopenia, percentage of bone marrow blasts, and bone marrow cytogenetics are the 3 primary prognostic factors in MDS. Other prognostic factors, such as marrow fibrosis, flow cytometry parameters, and somatic gene mutations, have been suggested as novel prognostic factors .
Genetic mutations are receiving increasing attention as prognostic factors, owing to the recent advent of inexpensive genome sequencing platforms . Most of the clinical and pathological features of MDS are believed to result from recurrent somatic genetic lesions , and genes such as
Quantitative reverse transcription PCR (qRT-PCR) assays of Wilms tumor gene 1 (
Polo-like kinase 1 (PLK1), a serine/threonine kinase, plays an important role in cell cycle regulation, particularly at the G2/M transition, as well as during mitosis and is encoded by
However, the role of
Patients who were newly diagnosed with MDS and sAML between March 2009 and March 2012 and who agreed to provide their BM samples for the study were screened, and only those patients whose samples were available for molecular analysis were enrolled. The study was approved by the institutional review board of Seoul St. Mary's Hospital, The Catholic University of Korea, and all patients and healthy controls enrolled in the study provided written informed consent before BM sample collection. Clinical and laboratory data at diagnosis or transformation to sAML and data on MDS treatment were obtained.
MDS was diagnosed according to the 2016 WHO classification . IPSS-R scores were calculated at MDS diagnosis . The extent of cytopenia, including absolute neutrophil count (ANC), hemoglobin levels, and platelet count, and cytogenetic risk groups were classified according to IPSS-R. Treatment responses after hypomethylating therapy (HMT) were assessed according to International Working Group 2006 criteria .
Total RNA was isolated from 5×106 mononuclear cells by using TRIzol Reagent (ThermoFisher Scientific, Waltham, MA, USA). cDNA was synthesized from 1 µg of total RNA in a 20 µL reaction mixture by using the Reverse Transcriptase kit (ThermoFisher Scientific) according to the manufacturer's instructions. Absolute quantification of the
The Statistical Package for the Social Sciences (SPSS, version 24.0, Inc., Chicago, IL, USA) was used for all statistical analyses. Continuous variables are presented as the median (range).
Sixty-seven patients with MDS were enrolled as well as 16 sAML patients. In 6 of the sAML patients, sAML evolved from MDS without any treatment, and in 10 of the patients, sAML evolved from MDS after HMT failure. Ten healthy controls were also included.
Table 1 summarizes the baseline characteristics of the MDS (N=67) and sAML (N=16) patients. The WHO subtypes of MDS were MDS unclassifiable (MDS-U, N=5), MDS with single lineage dysplasia (MDS-SLD, N=5), MDS with multilineage dysplasia (MDS-MLD, N=31), MDS with excess blast 1 (MDS-EB-1, N=13), and MDS with excess blast 2 (MDS-EB-2, N=13). The most common subtype of MDS was MDS-MLD, which was observed in 46.3% of the patients, followed by MDS-EB-1 and MDS-EB-2 at 19.4% each. sAML patients were classified into the natural course group (N=6) and the HMT failure group (N=10). The median age was 54 (16–77) years for the MDS patients and 58.5 (23–74) years for the sAML patients. The median percentage of BM blasts was 3% for MDS patients and 34% for sAML patients.
We compared the baseline
Patients were divided into 5 groups according to IPSS-R cytogenetic categories: very good, good, intermediate, poor, and very poor, which showed
Hematologic parameters, such as ANC, hemoglobin, and platelet count, were evaluated separately.
Loss of control over cellular proliferation is a hallmark of cancer . Owing to its essential roles in multiple steps of mitosis and the cellular responses to DNA damage and replication stress , PLK1 has been investigated in many different cancers.
In the present study,
Interestingly, patients who progressed from MDS to sAML after HMT failure showed remarkably higher
To the best of our knowledge, this is the first study to investigate the role of PLK1 in MDS, even though it has several limitations, including the relatively small number of patients enrolled and the fact that
Abbreviations: 18S rRNA, 18S ribosomal RNA; MDS, myelodysplastic syndromes;
Abbreviations: 18S rRNA, 18S ribosomal RNA; Int, intermediate; IPSS-R, Revised International Prognostic Scoring System;
Abbreviations: 18S rRNA, 18S ribosomal RNA; ANC, absolute neutrophil count; Int, intermediate; IPSS-R, Revised International Prognostic Scoring System; MDS, myelodysplastic syndromes;
Abbreviations: 18S rRNA, 18S ribosomal RNA;