Dr Wei on Next Steps for Elucidating the Role of HMAs on Megakaryocyte Maturation in MDS

"We are working on analyzing megakaryocytes from patients with MDS treated with HMAs [who have achieved] this platelet response to see whether we can confirm the results [from this study]… If that happens, these will be important findings to explain the biology of the platelet response in HMA treatment in patients.”

Yue Wei, PhD, an assistant professor in the Department of Leukemia, Division of Cancer Medicine, at The University of Texas MD Anderson Cancer Center, detailed planned research aiming to further clarify the role of hypomethylating agents (HMAs) in promoting late-stage megakaryocyte maturation and platelet production in patients with myelodysplastic syndrome (MDS).

Having previously used animal models to identify the biological mechanisms underlying the platelet response—specifically the role of TET2 mutations in promoting cell maturation—Wei and colleagues are now transitioning toward clinical validation in human cohorts.

The next step for this investigation involves performing sophisticated single-cell sequencing analyses to identify critical biomarkers and potential candidate genes that drive hematologic recovery, Wei explained. By analyzing megakaryocytes directly from samples of patients with MDS who have successfully achieved a clinical platelet response following HMA therapy, she hopes to confirm that the biological processes observed in their animal models are mirrored in humans.

Wei explained that identifying these specific marker genes is a prerequisite for developing next-generation translational approaches. This could include the identification of future therapeutic targets that can be combined with HMAs to intervene and potentially further improve platelet production for patients who currently experience limited responses, she added.

Wei and the research team at The University of Texas MD Anderson Cancer Center are determined to expand this study and are pursuing large-scale grants to support the transition from laboratory findings to comprehensive patient-level validation. She emphasized that confirming the biology of the platelet response in patient cohorts will provide the necessary evidence and confidence to move forward with targeted intervention strategies. Ultimately, these efforts aim to resolve critical questions regarding the improvement of HMA treatment for the megakaryocyte and platelet production fields, potentially leading to more effective management of severe cytopenias in high-risk MDS populations, Wei concluded.

Disclosures: Wei had no financial relationships to disclose.