Ruxolitinib Restores Normal Telomere Length in Patients with Myelofibrosis

Introduction Telomeres are specialized structures of repetitive nucleotide sequences that cap the ends of human chromosomes able to maintain genome stability and protect the cell from progressive DNA shortening. Some recent reports describe reduced telomere length in myelofibrosis (MF) regardless of hydroxycarbamide therapy, suggesting a possible prognostic relevance for this biomarker. As yet, no studies have investigated telomere dynamics following treatment with ruxolitinib. Methods Eight primary MF and 3 post ET MF patients were given 15 mg or 20 mg of oral ruxolitinib twice daily (BID) depending on baseline platelet counts. The drug dose was escalated to 25mg BID in patients with an inadequate response and reduced when platelet counts dropped to 50%, >50% bone marrow (BM) cellularity before and after treatment, pre and post treatment WHO scores for BM fibrosis of 3-4, duration of treatment >1000 days, total drug dose of >22 grams. Variables with a p-value lower than 0.2 in univariate analysis were included in multivariate analysis using a multi-step forward binary logistic regression model, where RLT >15% from baseline was considered a dependent variable. Only pre-treatment BM cellularity of >50% significantly correlated with >15% telomere elongation (p=0.004). Conclusion In our small cohort of patients, ruxolitinib proved capable of improving BM fibrosis and restoring telomere lengths to normal values. It is possible that ruxolitinib mediates modulation of the BM microenvironment, thereby stimulating stem cell hematopoiesis. It follows that peripheral blood telomere elongation could be indicative of the stem cellOs ability to self-renew. This finding, if confirmed, would open a debate about the rationale of treatment with telomerase inhibitors in MF patients. ![Figure][1] Figure Disclosures No relevant conflicts of interest to declare. [1]: pending:yes