Methods of monitoring therapeutic efficacy in a subject with MDS are provided. Also provided is a method of identifying a subject with myelodysplastic syndrome (MDS) for treatment with a telomerase inhibitor, and methods of treating MDS. The subject methods can include administering to the subject an effective amount of a telomerase inhibitor and assessing the hTERT expression levels in a biological sample obtained from the subject. In some cases, a 50% or greater reduction in hTERT expression level identifies a subject who has an increased likelihood of benefiting from treatment with the telomerase inhibitor. The subject can be naive to treatment with a HMA, lenalidomide, or both. In some cases, the subject is classified as having low or intermediate-1 IPSS risk MDS and/or MDS relapsed/refractory to Erythropoiesis-Stimulating Agent (ESA). In some instances, the telomerase inhibitor is imetelstat sodium.
