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Updated: Nov 26, 2025

In Situ Exploration of Murine Megakaryopoiesis using Transmission Electron Microscopy
Published on: September 8, 2021
Shared and Distinctive Ultrastructural Abnormalities Expressed by Megakaryocytes in Bone Marrow and Spleen From
Maria Zingariello1, Vittorio Rosti2, Alessandro M Vannucchi3
1Unit of Microscopic and Ultrastructural Anatomy, Department of Medicine, University Campus Bio-Medico, Rome, Italy.
Abstract:
Numerous studies have documented ultrastructural abnormalities in malignant megakaryocytes from bone marrow (BM) of myelofibrosis patients but the morphology of these cells in spleen, an important extramedullary site in this disease, was not investigated as yet. By transmission-electron microscopy, we compared the ultrastructural features of megakaryocytes from BM and spleen of myelofibrosis patients and healthy controls. The number of megakaryocytes was markedly increased in both BM and spleen. However, while most of BM megakaryocytes are immature, those from spleen appear mature with well-developed demarcation membrane systems (DMS) and platelet territories and are surrounded by platelets. In BM megakaryocytes, paucity of DMS is associated with plasma (thick with protrusions) and nuclear (dilated with large pores) membrane abnormalities and presence of numerous glycosomes, suggesting a skewed metabolism toward insoluble polyglucosan accumulation. By contrast, the membranes of the megakaryocytes from the spleen were normal but these cells show mitochondria with reduced crests, suggesting deficient aerobic energy-metabolism. These distinctive morphological features suggest that malignant megakaryocytes from BM and spleen express distinctive metabolic impairments that may play different roles in the pathogenesis of myelofibrosis.
Insights
Ultrastructural analysis reveals distinct megakaryocyte abnormalities in myelofibrosis patients. Bone marrow megakaryocytes show immature features and metabolic issues, while spleen megakaryocytes appear mature but have energy metabolism deficits.
Area of Science:
- Hematology
- Cell Biology
- Pathology
Background:
- Myelofibrosis is characterized by bone marrow fibrosis and extramedullary hematopoiesis, primarily in the spleen.
- Malignant megakaryocytes in the bone marrow exhibit ultrastructural abnormalities, but their morphology in extramedullary sites like the spleen remains understudied.
Purpose of the Study:
- To compare the ultrastructural morphology of megakaryocytes in the bone marrow and spleen of myelofibrosis patients versus healthy controls.
- To investigate potential differences in megakaryocyte metabolism and their implications in myelofibrosis pathogenesis.
Main Methods:
- Transmission electron microscopy was used to examine megakaryocytes from bone marrow and spleen samples.
- Samples were obtained from myelofibrosis patients and healthy individuals for comparative analysis.
Main Results:
- Megakaryocyte numbers were significantly increased in both bone marrow and spleen of myelofibrosis patients.
- Bone marrow megakaryocytes were predominantly immature with abnormal membranes and glycosome accumulation, suggesting altered metabolism.
- Spleen megakaryocytes were mature with normal membranes but showed mitochondrial abnormalities, indicating impaired energy metabolism.
Conclusions:
- Malignant megakaryocytes in myelofibrosis exhibit distinct ultrastructural and metabolic impairments in the bone marrow versus the spleen.
- These site-specific differences in megakaryocyte morphology and metabolism may contribute differently to the pathogenesis of myelofibrosis.

