The supportive effects of erythropoietin and mast cell growth factor on CD34+/CD36- sorted bone marrow cells of myelodysplasia patients.
In the present study, we analyzed the capacity of CD34+/CD36- sorted bone marrow cells of myelodysplasia patients (n = 4) to differentiate along the erythroid lineage in the presence of erythropoietin (Epo) and mast cell growth factor (MGF). Two subgroups could be identified. In 6 patients, a normal number of burst-forming units-erythroid (BFU-Es) were cultured from CD34+/CD36- sorted cells. Cells from these patients did have the capacity to differentiate to colony-forming units-erythroid (CFU-Es) progenitors in cell suspension cultures with Epo plus MGF followed by Epo in the culture assay. Moreover, the cells became CD34-/CD36+/gly-cophorin A (GpA)+ after 7 days of culture with Epo plus MGF, a pattern comparable to that of normal progenitors. In contrast, in 8 patients, a different pattern was observed. No BFU-Es or a low number of BFU-Es were cultured from the CD34+/CD36- sorted cell fraction that was, in most of the cases, incapable of differentiating to CFU-E progenitors. Flow cytometry of the sorted population showed that, after 7 days of culture with Epo plus MGF, a high proportion of CD34+/CD36- cells persisted, whereas a low proportion of cells became CD34-/CD36+/GpA+. The unresponsiveness is not caused by the used growth factor combination, because the addition of interleukin-3 did not correct the defect. Evi-1 expression was studied in 9 cases to show whether an aberrant Evi-1 expression correlates with a disturbed erythroid development. Evi-1 expression was shown in 4 of 9 cases, whereas 3 of 9 cases did have a disturbed erythroid differentiation. In summary, the results show that the defects in the erythroid development in a subpopulation of patients with myelodysplasia is localized at an early stage of the erythroid differentiation and is associated with the persistent expression of the CD34 antigen and, in some cases, with the expression of Evi-1.
Brada
S
S
Department of Hematology, University Groningen, The Netherlands.
de Wolf
J
J
Hendriks
D
D
Esselink
M
M
Ruiters
M
M
Vellenga
E
E
D018952:Antigens, CD34 / Q000032:analysis; D001483:Base Sequence; D001853:Bone Marrow / Q000473:pathology*; D018955:CD36 Antigens / Q000032:analysis; D002454:Cell Differentiation; D002455:Cell Division; D002469:Cell Separation; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D004920:Erythropoiesis / Q000187:drug effects; D004921:Erythropoietin / Q000494:pharmacology*; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D018922:HL-60 Cells / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D006801:Humans; D000074008:MDS1 and EVI1 Complex Locus Protein; D008969:Molecular Sequence Data; D009190:Myelodysplastic Syndromes / Q000473:pathology*; D011519:Proto-Oncogenes; D019089:Stem Cell Factor / Q000494:pharmacology*; D014157:Transcription Factors
D018952:Antigens, CD34; D018955:CD36 Antigens; D004268:DNA-Binding Proteins; D000074008:MDS1 and EVI1 Complex Locus Protein; C063575:MECOM protein, human; D019089:Stem Cell Factor; D014157:Transcription Factors; D004921:Erythropoietin