ADENOVIRAL MEDIATED GENE-TRANSFER CAN BE ACCOMPLISHED IN HUMAN MYELOID CELL-LINES AND IS INHIBITED BY ALL-TRANS-RETINOIC ACID-INDUCED DIFFERENTIATION

Background and Objective. Gene transfection could potentially represen t a useful therapeutic tool for genetic and neoplastic hematological d iseases. After having long been considered poorly able to transfect my eloid cells, adenoviral vectors have recently been demonstrated to be capable of introducing foreign DNA into purified CD34(+) cells from hu man bone marrow or cord blood. In the present study we evaluated the f easibility of adenoviral-mediated gene transfer in two human leukemic cell lines, both at baseline and after differentiation induction by al l-trans retinoic acid (ATRA). Methods. We used a recombinant adenoviru s expressing beta-galactosidase (Ad-RSV-beta-gal) to transfect K562 an d HL-60 cell lines. The effects of 10(6)M ATRA were evaluated after 8 days of exposure. The efficacy of transfection was verified by X-gal s taining. Results. Ad-RSV-beta-gal was able to transfect both the HL-60 and, to a minor extent, the K562 cell lines. The addition of ATRA had no effect on transfection of K562 cells, while a lower percentage of beta-gal-positive cells was detected in HL-60, which underwent differe ntiation upon ATRA treatment. Interpretation and Conclusions. These da ta suggest that adenoviral-mediated gene transfer could be feasible in myeloid leukemia cell lines and that it is inhibited by ATRA in diffe rentiation-sensitive cells. The latter effect merits further investiga tion in order to verify whether this represents an ATRA-related or a d ifferentiation-related phenomenon.