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Stimulation of CFU-Mk colony growth by normal plasma and plasma from myelodysplastic patients
1Department of Haematology, University of Wales College of Medicine, Heath Park, Cardiff, U.K.
Abstract:
The ability of plasma from myelodysplastic patients to support the clonal growth of normal megakaryocyte progenitors (CFU-Mk) was compared with that of plasma from normal subjects. The resultant megakaryocyte colonies were expressed as a plasma factor index megakaryocyte (PFI-Mk). All cultures included PHA-LCM and medium conditioned by the human bladder carcinoma cell line 5637, and some of them had EPO. PFI-Mk (MDS) was significantly lower than PFI-Mk (normal), both with and without EPO. A positive correlation was found between megakaryocyte and platelet count in normal subjects, but was not present in MDS patients. There was no correlation between platelet count and PFI-Mk in neither group. In MDS there was a negative correlation between megakaryocyte number and PFI-Mk, both with and without EPO. Although, the mean megakaryocyte number in MDS and in normal bone marrow was similar, the proportion of immature megakaryocytes was much higher in MDS. Previous work indicates an abnormal clonal origin of megakaryocytes in MDS. The present study suggests that abnormal plasma factors affects megakaryocytopoiesis in this condition.
Insights
Plasma from myelodysplastic syndrome (MDS) patients impairs normal megakaryocyte progenitor growth. Abnormal plasma factors, not platelet counts, negatively impact megakaryocytopoiesis in MDS.
Area of Science:
- Hematology
- Cell Biology
- Oncology
Background:
- Myelodysplastic syndromes (MDS) are a group of clonal hematopoietic stem cell disorders.
- Megakaryocytopoiesis, the process of megakaryocyte development, is often dysregulated in MDS.
- Previous research suggests an abnormal clonal origin of megakaryocytes in MDS.
Purpose of the Study:
- To compare the ability of plasma from MDS patients and normal subjects to support normal megakaryocyte progenitor growth.
- To investigate the relationship between plasma factors, megakaryocyte counts, and platelet counts in MDS.
- To assess the impact of plasma factors on megakaryocytopoiesis in MDS.
Main Methods:
- Plasma from MDS patients and normal subjects was used to culture normal megakaryocyte progenitors (CFU-Mk).
- Megakaryocyte colonies were quantified using a plasma factor index megakaryocyte (PFI-Mk).
- Cultures were performed with and without EPO (erythropoietin) and included PHA-LCM and 5637 cell line conditioned medium.
Main Results:
- Plasma factor index megakaryocyte (PFI-Mk) was significantly lower in MDS patients compared to normal subjects, with or without EPO.
- A positive correlation between megakaryocyte and platelet count was observed in normal subjects but not in MDS patients.
- In MDS, a negative correlation was found between megakaryocyte number and PFI-Mk, irrespective of EPO presence.
Conclusions:
- Abnormal plasma factors in MDS patients negatively affect megakaryocytopoiesis.
- The findings suggest that plasma-derived factors play a significant role in the megakaryocytopoiesis abnormalities seen in MDS.
- While mean megakaryocyte numbers may be similar, MDS bone marrow shows a higher proportion of immature megakaryocytes, indicating dysregulated development.