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Early circulating erythroid progenitors (BFU-E) in sickle cell anemia
1Albert Einstein College of Medicine, Bronx, New York 10461.
Experientia
|February 15, 1993
Summary
Sickle cell anemia patients with low fetal hemoglobin (HbF) levels show increased BFU-E activity and constitutive GM-CSF production. High HbF levels correlate with inhibitory factors and distinct BFU-E responses.
Area of Science:
- Hematology
- Molecular Biology
- Genetics
Background:
- Sickle cell anemia (SS) patients exhibit heterogeneous peripheral blood fetal hemoglobin (HbF) levels, influencing disease pathophysiology.
- Two distinct subpopulations exist: low HbF (LFSS) with high burst-forming unit-erythroid (BFU-E) activity and high HbF (HFSS) with normal BFU-E characteristics.
- Further heterogeneity is observed in growth factor responsiveness and adherent cell activity between LFSS and HFSS groups.
Purpose of the Study:
- To investigate the distinct characteristics of BFU-E and adherent cells in LFSS versus HFSS patients.
- To elucidate the role of growth factors like GM-CSF and IL-3 in regulating BFU-E proliferation in sickle cell anemia.
- To understand the factors contributing to the heterogeneity of BFU-E regulation in sickle cell disease.
Main Methods:
- Analysis of peripheral BFU-E numbers and DNA synthesis.
- Assessment of burst promoting activity (BPA) release by low-density (LD) adherent cells.
- Culture experiments involving monocyte-derived cells and conditioned media (CM) from SS patients.
- Evaluation of BFU-E responsiveness to granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-3 (IL-3).
Main Results:
- LFSS patients display increased circulating BFU-E in active synthesis, with BPA release from unstimulated LD adherent cells.
- HFSS patients have normal BFU-E numbers, with LD cells not releasing BPA; their CM inhibits BFU-E expression.
- LFSS BFU-E are equally responsive to GM-CSF and IL-3, while HFSS BFU-E include a subset exclusively dependent on IL-3, similar to normal individuals.
Conclusions:
- LFSS patients exhibit an actively proliferating BFU-E population regulated by constitutive GM-CSF and potentially other factors.
- HFSS patients' adherent cells may release inhibitory factors, contributing to distinct BFU-E regulation.
- BFU-E heterogeneity in sickle cell disease appears to be an epiphenomenon of HbF levels, reflecting varying hemopoietic stress.