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(-) sort ed bone marrow cells of myelodysplasia patients (n = 4) to differentia te 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 unit s-erythroid (CFU-Es) progenitors in cell suspension cultures with Epo plus MGF followed by Epo in the culture assay. Moreover, the cells bec ame CD34(-)/CD36(+)/glycophorin A (GpA)(+) after 7 days of culture wit h 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(-) sorte d cell fraction that was, in most of the cases, incapable of different iating to CFU-E progenitors. Flow cytometry of the sorted population s howed that, after 7 days of culture with Epo plus MGF, a high proporti on of CD34(+)/CD36(-) cells persisted, whereas a low proportion of cel ls became CD34(-)/CD36(+)/GpA(+). The unresponsiveness is not caused b y the used growth factor combination, because the addition of interleu kin-3 did not correct the defect. Evi-1 expression was studied in 9 ca ses to show whether an aberrant Evi-1 expression correlates with a dis turbed erythroid development. Evi-1 expression was shown in 4 of 9 cas es, whereas 3 of 9 cases did have a disturbed erythroid differentiatio n. In summary, the results show that the defects in the erythroid deve lopment in a subpopulation of patients with myelodysplasia is localize d 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. (C) 1996 by The American Society of He matology.