RETROVIRAL TRANSFER OF THE N1SLACZ GENE INTO HUMAN CD34(-POPULATIONS AND INTO TF-1 CELLS - FUTURE-PROSPECTS IN GENE-THERAPY() CELL)

Few data are available concerning behavior of reimplanted human hemato poietic cells after autologous stem cell transplantation. This paper r eports the possibility to transfer gene markers coding for beta-galact osidase (beta-Gal) activity by retroviral vectors into a human leukemi c growth factor-dependent cell line, TF-1, and into human hematopoieti c progenitors isolated from peripheral blood or bone marrow. Using var ious combinations of retroviral vectors and packaging cell lines, we d emonstrated high expression of a bacterial beta-Gal activity induced b y the LacZ gene, the nlsLacZ gene, or the Sh-ble/LacZ gene, in human h ematopoietic cells. The expression of the nlsLacZ construct was stable until the end of the culture in infected CD34(+) cell-enriched cell p opulations, and a slow decrease of transgene expression was observed i n a transduced TF-1 cell population during a 1-year long-term culture. Data obtained with the nlsLacZ gene demonstrate that both retroviral transfer and corresponding gene expression were not found to modify th e pattern of cell proliferation and differentiation. These results ope n interesting prospectives for the use of the nlsLacZ gene to mark and follow the fate of progenitor cells isolated from patients with cance rs prior to reimplantation.