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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: BACKGROUND, METHODS, RESULTS. Meshes: Adult, Aged, Antigens, CD34, Apoptosis, Blotting, Western, Bone Marrow Cells, CCAAT-Enhancer-Binding Protein-alpha, Cell Differentiation, Cell Proliferation, Cells, Cultured, Gene Expression, Granulocyte Colony-Stimulating Factor, Hematopoietic Stem Cells, Humans, Imidazoles, Immunohistochemistry, Inhibitor of Differentiation Protein 1, Middle Aged, Myelodysplastic Syndromes, Neutrophils, Proto-Oncogene Proteins c-akt, Pyridines, STAT5 Transcription Factor, Time Factors, Transfection, Tumor Suppressor Proteins, p38 Mitogen-Activated Protein Kinases.
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Is ectopic expression of C/EBPalpha and ID1 sufficient to restore defective neutrophil development in low-risk myelodysplasia? Context: In patients with myelodysplasia, a general defect in the multipotent stem-cell compartment results in disturbed proliferation and differentiation of the erythroid, megakaryocytic and myeloid lineages. Although a number of genetic defects in myelodysplastic progenitor cells have been described, the intracellular signaling pathways underlying aberrant regulation of myelopoiesis remain relatively undefined. Here, an ex vivo differentiation system was used to selectively screen for molecules improving defective hematopoiesis in myelodysplastic CD34(+) progenitor cells. Bone marrow-derived CD34(+) cells isolated from patients with low-risk myelodysplastic syndrome showed impaired capacity to proliferate and differentiate as well as increased levels of apoptosis. In an attempt to improve the expansion and differentiation of the myelodysplastic CD34(+) progenitors, cells were treated with the p38MAPK pharmacological inhibitor SB203580, or retrovirally transduced to ectopically express active protein kinase B (PKB/c-akt), or the transcriptional regulators STAT5, C/EBPalpha or ID1. Whereas treatment of progenitors with SB203580, PKB or STAT5 did not enhance neutrophil development, ID1- and C/EBPalpha-transduced cells exhibited increased granulocyte/macrophage colony formation. Furthermore, ectopic expression of C/EBPalpha resulted in improved neutrophil maturation.
assistant
These data suggest that targeting the ID1 and C/EBPalpha transcriptional regulators may be of benefit in the design of novel therapies for low-risk myelodysplasia. Final Decision: yes