Team Telomere is thrilled to share highlights from our participation at the 2024 American Society of Hematology (ASH) Annual Meeting! We attended several impactful TBD-relevant poster and oral presentations and are excited to bring you research summaries from these sessions:
Application of Machine Learning in the Diagnostic Work-up of Telomere Biology Disorders
In this study, the authors explored how machine learning can be applied to improve the diagnosis of Telomere Biology Disorders (TBDs). The researchers analyzed data from 140 patients, including clinical, biochemical, and genetic features, and applied machine learning to identify potential TBD diagnoses. One of the models achieved a 75% accuracy in predicting TBD. Another model created “clusters,” with clusters 1 and 2 showing a strong prevalence of TBD features such as telomere length and skin findings classically seen in TBDs. The authors note that these findings suggest that machine learning can help reclassify undiagnosed or misdiagnosed patients, improve the diagnostic process for TBD, and identify individuals who may benefit from further genetic testing and follow-up.
Engineered Telomerase RNA Component (eTERC), a Potential Lncrna Medicine to Extend Replicative Lifespan and Telomere Length in Dyskeratosis Congenita Patient Stem Cells
This study investigated a new synthetic RNA-based approach called engineered TERC (eTERC). By modifying the RNA component of telomerase, the study’s researchers observed significant telomere lengthening and extended the replicative lifespan of cells. In addition, eTERC was applied to patient-derived stem cells from TBD patients carrying common TBD mutations (e.g. TERT, TERC, RTEL1, DKC1, TINF2, and PARN). After a single application, telomeres initially lengthened but eventually returned to their baseline, showing a temporary increase in the ability for the cells to divide and renew themselves while still keeping their normal regulatory mechanisms. These findings shine light on exciting potential therapeutic directions for the field of TBDs.
Danazol Treatment for Telomere Biology Disorders: Long-Term Results of a Phase I/II Study
In this study, authors studied the long-term follow-up of danazol in treating TBDs. The study followed 26 patients treated with 800 mg of danazol daily for two years. Results showed that danazol improved blood counts in most patients. Telomere length was studied using flow-FISH during danazol treatment in a subset of patients. The authors observed that telomere length remained stable, with a rate of loss comparable to that of healthy individuals. The study also evaluated whether danazol impacted the progression of pre-malignant or cancer-associated mutations (i.e. clones). Based on the study’s findings, these mutations appeared largely stable during the treatment and follow-up period. Additionally, the study found no new solid cancers during treatment. The study found that many patients needed to continue or restart danazol after the trial to help support their blood counts. These findings help better understand the long-term impacts of danazol in TBDs.
Natural History and Predictors of Survival in Adult Patients with Telomere Biology Disorders (TBDs)
This study explored the natural history and factors predicting survival in adult patients with TBDs. Among the adults in this cohort, common clinical features included interstitial lung disease (ILD) in 66%, bone marrow failure (BMF) in 32%, cirrhosis or hepatic fibrosis in 38%, and bone disease in 70%. The study found ILD to significantly predict survival in adults with TBD. The authors highlight that these findings emphasize the need for focused therapies for ILD in adult TBD to improve outcomes and alter the natural history of the disease.
T Lymphopenia and Aged Immune System Characterize Immunodeficiency in Adult Patients with Telomere Biology Disorders
In this study, the authors explored the immunodeficiency in TBDs by studying 88 adult patients with TBDs. Around 36% of the patients experienced significant infections, including recurrent or severe infections that required hospitalization. Of note, low T cell counts (T lymphopenia) were strongly linked to these infections. Patients with low B cell counts (B cell lymphopenia) were seen to have recurrent infections. Lower absolute lymphocyte counts and T cell markers (such as CD3, CD4, CD8) were linked to worse survival outcomes. The study also identified signs of accelerated aging in the immune system, for example, having fewer naïve T cells and more memory and effector T cells, which resemble an “aged” immune profile. These findings provide insights into the clinical presentations of TBDs, which can improve our management and treatment approaches.
Thank you to all our researchers for your dedication to creating brighter futures for our TBD community.