Dr Wei on the Correlation Between TET2 Mutations and Platelet Response in MDS

"The study of platelet response has multiple [implications for our understanding of] the mechanisms of the disease, the therapy for the disease, and even the improvement of HMA treatment."

Yue Wei, PhD, an assistant professor in the Department of Leukemia, Division of Cancer Medicine, at The University of Texas MD Anderson Cancer Center, discussed the rationale for evaluating platelet responses in patients with myelodysplastic syndromes (MDS) treated with hypomethylating agents (HMAs) in a longitudinal analysis.

HMAs represent the primary therapeutic class for patients with MDS, and investigators have frequently observed that an improvement in thrombocytopenia—referred to as the platelet response—is a significant indicator of treatment efficacy, Wei began.

According to Wei, this response is not only a clinical milestone but is also closely associated with a favorable prognosis for those undergoing therapy.

From a translational perspective, the longitudinal analysis aimed to uncover the biological drivers behind these improvements. The study identified a significant link between the TET2 mutation and the likelihood of achieving a platelet response. TET2 is recognized as one of the most prevalent and critical mutations in the MDS landscape; accordingly, understanding its interaction with HMAs is vital for refining management strategies, Wei asserted. Because of the inherent difficulties in studying thrombocytopenia mechanisms directly through patient samples, Wei and colleagues utilized a TET2 knockout mouse model to accurately simulate the disease and study the relationship between therapy and platelet improvement.

The results of this analysis were presented at the 2025 ASH Annual Meeting, and offer valuable insights into the underlying biology of the disease and the mechanisms by which HMAs modify the hematologic environment, Wei concluded.

Disclosures: Wei had no financial relationships to disclose.