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Apoptotic megakaryocyte dysplasia in the myelodysplastic syndromes
S J Hatfill1, E D Fester, J G Steytler
1Department of Hematological Pathology, Tygerberg Hospital, Republic of South Africa.
Abstract:
The terminal phase of the megakaryocyte life span is characterized by the onset of apoptosis to form compact, denuded megakaryocyte nuclei (DMK) surrounded by a thin rim of cytoplasm. Increased numbers of DMK have been reported in patients with acquired immune deficiency syndrome (AIDS) and chronic myeloproliferative disorders. In this study the bone marrow biopsies of 20 patients with various FAB subtypes of myelodysplastic syndrome (MDS) were examined for the presence of DMK cells and semiquantified for marrow reticulin level. For all MDS subtypes, a 9% or greater incidence of DMK in the total megakaryocyte population of the bone marrow was associated with a significant deposit of reticulin in the marrow. Immunocytochemical staining for Factor VIII (Von Willebrand factor), showed the abnormal deposition of this megakaryocyte protein in the extravascular stroma around many of the DMK cells. These findings are consistent with a hypothesis for excess stromal reticulin based on the defective maturation and intramedullary death of large numbers of megakaryocytes. The number of DMK in the marrow biopsies of MDS patients may have prognostic significance.
Insights
Denuded megakaryocyte nuclei (DMK) indicate defective maturation in myelodysplastic syndrome (MDS). High DMK incidence correlates with increased marrow reticulin, suggesting prognostic value in MDS patients.
Area of Science:
- Hematology
- Oncology
- Cell Biology
Background:
- Megakaryocyte apoptosis culminates in denuded megakaryocyte nuclei (DMK).
- Elevated DMK counts are observed in acquired immune deficiency syndrome (AIDS) and myeloproliferative disorders.
- Myelodysplastic syndromes (MDS) are a group of clonal hematopoietic stem cell disorders.
Purpose of the Study:
- To investigate the presence and significance of DMK in myelodysplastic syndromes (MDS).
- To correlate DMK incidence with bone marrow reticulin levels and Factor VIII deposition in MDS patients.
Main Methods:
- Bone marrow biopsies from 20 MDS patients (various FAB subtypes) were analyzed.
- DMK cell presence was quantified relative to the total megakaryocyte population.
- Marrow reticulin levels were semiquantified.
- Immunocytochemical staining for Factor VIII (Von Willebrand factor) was performed.
Main Results:
- A 9% or greater incidence of DMK in MDS patients was associated with significant reticulin deposition in the bone marrow.
- Abnormal deposition of Factor VIII was observed in the extravascular stroma surrounding DMK cells.
- Findings support a hypothesis of excess stromal reticulin due to defective megakaryocyte maturation and intramedullary death.
Conclusions:
- The number of DMK cells in MDS bone marrow biopsies may possess prognostic significance.
- Defective megakaryocyte maturation and death contribute to stromal reticulin excess in MDS.
- Further research into DMK as a prognostic marker in MDS is warranted.