Chromosomal Abnormalities in MDS Are Linked to Dysregulation of CDC20 and CEP55 Genes

Myelodysplastic syndrome (MDS) is a clonal hematopoietic disorder characterized by cytopenias and an increased risk of progression to acute myeloid leukemia (AML). Its pathogenesis is strictly linked to chromosomal instability, which in turn provides a valuable prognostic marker. Malignant cells develop alternative routes to escape mitosis checkpoints, overcoming the mitotic arrest imposed by Spindle Assembly Checkpoint (SAC), a process dependent on CDC20 inactivation. Abnormal levels of CDC20 can inhibit mitotic arrest, promoting premature exit from mitosis. Overexpression of CEP55 also facilitates the mitotic exit, resulting in polyploidy (an event called Mitotic Slippage). Since chromosomal abnormalities are one of the most important prognostic factors for patients with MDS, this study aimed to analyze the possible link between chromosomal abnormalities and CDC20 and CEP55 mRNA expression in MDS. We evaluated the bone marrow cells from 45 patients diagnosed as MDS according to 2016 WHO-classification (1 MDS-SLD, 15 MDS-RS-MLD, 5 MDS-MLD, 1 t-MDS, and 23 MDS-EB) and 5 bone marrow of healthy controls. Conventional Karyotyping was performed by G-banding of 20 metaphases whenever possible. TaqMan expression assays for CDC20 (Hs00426680_mH) and CEP55 (Hs01070181_m1) were performed in duplicate and the expression ratios were calculated using the 2−ΔCq method. Normality was evaluated by Shapiro-Wilk test. Outliers were removed. The Student’s t-test or one-way ANOVA with Tukey/Games Howell post-hoc test was used to analyze the influence of relative expression regarding variables. Patients with MDS showed increased expression of CDC20 and CEP55 compared to healthy individuals (p Our data suggest CDC20 and CEP55 as possible new therapeutic targets in MDS. There is a need for further studies, validations and urgent in-depth investigations in cell lines/primary samples or murine models. Download : Download high-res image (323KB) Download : Download full-size image Disclosures No relevant conflicts of interest to declare.