GM-CSF Stimulates Blast Cell Proliferation in Long-Term Culture of Bone Marrow from Patients with Myelodysplasia

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Abstract
In long-term culture (LTBMC) of marrow from patients with myelodysplastic syndromes (MDS) abnormal patterns of growth, dysplastic cell morphology and cytogenetic changes present at initiation of culture persisted, providing a model in which to investigate the effects of hemopoeitic growth factors. In this model, rGM-CSF added weekly (100 µ/ml) failed to increase the number of non-adherent cells, adherent cells or CFU-GM, but markedly increased the number or blast cells (from 11 ± 5%) to 44 ± 6% after 3.5 weeks), with a commensurate fall in the numbers of mature myeloid cells. In contrast, in LTBMC of normal marrow, rGM-CSF increased the non-adherent cell count by almost 5-fold. The increase was almost entirely due to enhanced production of myeloid precursors, predominantly mature myeloid cells, with a small increment in CFU-GM (2 fold: p < 0.05). These results suggest that in MDS GM-CSF enhances the “differentiation block” and may accelerate leukemic transformation.