Objective Myelodysplastic syndrome (MDS) is a malignant clonal disorder of hematopoietic stem cells which is characterized by morphologic dysplasia. However, the pathological characteristics of megakaryocytes (MKs) in MDS patients with gene mutation are not well established.

Methods Bone marrow MK specimens from 104 patients with primary MDS were evaluated, and all patients were distributed into two groups according to gene mutation associated with functional MKs. The morphologic and cellular characteristics of MKs and platelets were recorded and compared.

Results The more frequently mutated genes in MDS patients were TUBB1 (11.54%), VWF (8.65%), NBEAL2 (5.77%), and the most common point mutation was TUBB1 p.(R307H) and p.(Q43P). Patients with MK mutation showed a decrease in adenosine diphosphate-induced platelet aggregation, high proportion of CD34+ CD61+ MKs (10.00 vs. 4.00%, p = 0.012), and short overall survival (33.15 vs. 40.50 months, p = 0.013). Further, patients with a higher percent of CD34+ CD61+ MKs (≧20.00%) had lower platelet counts (36.00 × 109/L vs. 88.50 × 109/L, p = 0.015) and more profound emperipolesis (p = 0.001). By analyzing RNA-sequencing of MKs, differentially expressed mRNA was involved in physiological processes including platelet function and platelet activation, especially for MDS patients with high percent of CD34+CD61+MKs. The high levels of expression of CD62P, CXCL10, and S100A9 mRNA, shown by RNA sequencing, were validated by PCR assay.

Conclusion High proportion of CD34+ CD61+ MKs was a poor prognostic factor in MDS patients with MK mutation. CD62P, CXCL10, and S100A9 may be the potential targets to evaluate the molecular link between gene defects and platelet function.

J.M.L. performed the research and wrote the manuscript. Y.L.L. assisted in performing the research. F.X.L. and J.L.Z. assisted in analyzing the data and writing the manuscript. Z.P.P.; J.L.Z.; R.A.; and Y.B.C. assisted in the data analysis.

All authors approved the submission of the paper.

Data will be made available on request.

*Fangxiu Luo and Jialu Zhao contributed equally to this work.

Article published online:
10 June 2024

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