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CC BY 4.0 · Glob Med Genet 2024; 11(02): 187-195
DOI: 10.1055/s-0044-1787752
Original Article

Clinical and Molecular Characteristics of Megakaryocytes in Myelodysplastic Syndrome

Fangxiu Luo   *
3   Department of Pathology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
,
Jialu Zhao   *
1   Department of Laboratory Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
,
Yubao Chen
4   Department of Hematology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
,
Zhenping Peng
1   Department of Laboratory Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
,
Ran An
4   Department of Hematology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
,
Yeling Lu
1   Department of Laboratory Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
,
Jiaming Li
1   Department of Laboratory Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
2   Transfusion Department, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
› Author Affiliations Funding This work was supported in part by grants from the National Natural Science Foundation of China (No.82070194 and No.8237022).
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Abstract

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.

Keywords

MDS - CD34 - MK - CD62P - emperipolesis - TUBB1

Author Contribution Statement

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.


Consent for Publication

All authors approved the submission of the paper.


Data Availability Statement

Data will be made available on request.


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




Publication History

Article published online:
10 June 2024

© 2024. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

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