Abstract
Background: Aplastic anemia (AA) is a rare bone marrow failure syndrome characterized by notably short telomere length, which is associated with treatment responses. In this study, we measured telomere lengths in Korean pediatric AA patients using flow-fluorescence in situ hybridization (Flow-FISH) and explored their shortening in relation to disease characteristics, genetic conditions and patient outcomes. Methods: We analyzed peripheral blood samples from 75 AA patients and 101 healthy controls. Telomere lengths were measured using Flow-FISH, and relative telomere length (RTL) and delta RTL assessments were conducted. Genetic evaluations included karyotyping, chromosome breakage tests and clinical exome sequencing (CES) to identify inherited bone marrow failure syndrome (IBMFS)-associated genetic variants. Results: Telomere lengths in AA patients were significantly lower than those of age-adjusted healthy controls. Patients receiving immunosuppressive therapy tended to have long telomeres, as indicated by high delta RTL values. Patients with genetic abnormalities, including karyotype abnormalities (n = 2) and genetic variants (n = 11) such as carrier genes of IBMFS or variants of unclear significance, showed significantly short telomere lengths. Conclusions: This study reinforces the importance of telomere length as a biomarker in acquired AA. Utilizing Flow-FISH, we were able to accurately measure telomere lengths and establish confidence in this method as an appropriate laboratory test. We found significant reduction in telomere lengths in AA patients, and importantly, longer telomeres were correlated with better outcomes in immunosuppressive therapy. Additionally, our genetic analysis underscored the relevance of variants in IBMFS-associated genes to the pathophysiology of short telomeres.