HOXB4 confers a constant rate of in vitro proliferation to transduced bone marrow cells.

摘要: HOXB4 overexpression mediates increased self-renewal of haematopoietic stem cells (HSCs) ex vivo. Since HOXB4-expanded HSCs retain normal differentiation potential and there is no leukaemia development from transduced HSCs, represents a promising tool for human HSC therapy. However, the proliferation capacity overexpressing fibroblasts resulting upregulation JunB, Fra-1 cyclin D1 protein levels may indicate risk associated with approach. This prompted us to investigate rate, expression cell cycle regulators directly in bone marrow cultures HOXB4. Here we show that comparison neo-transduced control cultures, HOXB4-overexpressing had more homogenous morphology numbers progenitor capable generate primitive colonies vitro. In contrast, long-term showed hallmarks myeloid reduced secondary colony forming activity. We further multilineage repopulating activity vivo, which was present only declined over time. vitro did not result an increase but stabilization rate (1.4-1.8 divisions per day), while gradually declined. Correspondingly, paralleled by decreased cyclins, CDKs AP-1 family members. These results suggest growth HOXB4- compared remains constant along suppression differentiation. contrast fibroblasts, engineered overexpress do upregulate complex members or cyclins indicating acts type-specific way.