Telomere erosion can lead to genomic instability and cancer progression. It has been suggested that the shortest telomere, not the average telomere length (TL), is critical for cell viability. Some studies have shown shorter TL in myelodysplastic syndrome (MDS) patients but the critically short telomeres, the variability of TL within individual patient has not been evaluated. Thus, we aimed to investigate the TL of MDS patients and assessed the association of TL with recurrent genetic mutations in MDS. We measured the TL of bone marrow nucleated cells for diagnostic samples at a single-cell level by quantitative fluorescence in situ hybridization (Q-FISH) for 58 MDS patients and analyzed the minimum, median, average, standard deviation, average of the 0th to 10th percentile TL within a patient, and the proportion of cells with TL that is shorter than the lowest 10th percentile of the normal control (NC). The correlations of TL to clinical parameters, cytogenetic results, and genetic mutations were assessed. MDS patients showed eroded telomeres and narrow distribution compared to the NC (P < 0.001, P = 0.018, respectively). Patients with mutation showed significantly lesser cells with short TL, below the lowest 10th percentile of the NC (P = 0.017), but no differences in TL were found according to mutations/cytogenetic abnormalities except for CSF3R mutation. However, those patients with a high percentage (≥80 %) of cells with short TL showed poorer overall survival (P = 0.021), and this was an independent prognostic factor, along with TP53, U2AF1 mutation, and high BM blast count (P = 0.044, 0.001, 0.004, 0.012, respectively). The shortest TL, which determines the fate of the cell, was significantly shorter, and higher burden of cells with short TL were found in MDS, which correlated with poor survival, suggesting the need to measure TL in single cells by Q-FISH.

Statins not only have a lipid-lowering effect but also reduce inflammation and have an antithrombotic effect. Since hypercoagulability assessed by thrombin generation assay (TGA) and increased formation of neutrophil extracellular traps (NET) were demonstrated in diabetes, we investigated whether statin therapy in diabetes modifies coagulation status and NET formation. Twenty-five consecutive patients with diabetes were recruited. Global coagulation assays (prothrombin time [PT], activated partial thromboplastin time [aPTT], and TGA) and NET markers (DNA–histone complex, cell-free DNA, and neutrophil elastase) were measured before and after 3-month moderate-intensity statin therapy. In addition, all coagulation factors and 3 anticoagulation factors were measured. Statin therapy significantly reduced endogenous thrombin potential (ETP) value and blood lipids but did not change the PT and aPTT values or NET formation markers. Statin significantly decreased not only coagulation factors (II, V, VIII, IX, and X) but also the anticoagulation factor antithrombin. Statin-induced reduction of factor V and X significantly contributed to the reduction of ETP value. The extent of reduction in coagulation factors correlated with that of anticoagulation factors, but not that of cholesterol. It is possible to use TGA as a global coagulation assay that can detect coagulation status modified by statin therapy. Additional studies are needed to evaluate the clinical implications of statin-induced simultaneous reduction of coagulation and anticoagulation factors.