Dr Wei on Platelet Responses With HMAs in Patients With MDS

"This patient cohort [showed] the potential involvement of TET2 compared with other common mutations in [MDS]. This has not been published before. We need to verify the results, but they give us important hints about the clinical value of this mutation...”

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 findings from a longitudinal analysis evaluating platelet responses and megakaryocyte maturation in patients with myelodysplastic syndromes (MDS) treated with hypomethylating agents (HMAs).

The analysis focused on a cohort of 390 patients with MDS who were treated with single-agent HMA therapy, Wei detailed. Results from the analysis presented during the 2025 ASH Annual Meeting, showed that significant platelet count recovery typically manifests at approximately days 65 to 70 of treatment. However, this response was not universal; it was observed only in the subset of patients with disease harboring TET2 mutations who also presented with severe baseline thrombocytopenia, defined as a platelet count below 33 x 10⁹/L.

Wei underscored that these results show the potentially unique role of TET2 in the mechanism of MDS compared with other common mutations associated with the disease, many of which were present in the same clinical cohort. This specific correlation between a molecular marker and a functional platelet response is a novel finding that provides important clues regarding the clinical value of the TET2 mutation, Wei said.

Because of the complication of studying thrombocytopenia, and the need to bridge these clinical observations with biological understanding, Wei and colleagues then utilized established TET2 knockout mouse models.By utilizing these animal models, investigators can simulate the disease environment, apply HMAs, and study the resulting platelet changes in detail, Wei explained. She noted that having an available animal model allows the team to investigate the underlying biology and test potential biomarkers or new therapeutic approaches before moving to clinical settings. Ultimately, this research provides a vital framework for verifying clinical outcomes and optimizing HMA-based treatment strategies for patients with high-risk molecular profiles, Wei concluded.