Adenoviral mediated gene transfer can be accomplished in human myeloid cell lines and is inhibited by all-trans retinoic acid-induced differentiation

Abstract

BACKGROUND AND OBJECTIVE: Gene transfection could potentially represent a useful therapeutic tool for genetic and neoplastic hematological diseases. After having long been considered poorly able to transfect myeloid cells, adenoviral vectors have recently been demonstrated to be capable of introducing foreign DNA into purified CD34+ cells from human bone marrow or cord blood. In the present study we evaluated the feasibility of adenoviral-mediated gene transfer in two human leukemic cell lines, both at baseline and after differentiation induction by all-trans retinoic acid (ATRA). METHODS: We used a recombinant adenovirus expressing beta-galactosidase (Ad-RSV-beta-gal) to transfect K562 and 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 staining. 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 differentiation upon ATRA treatment. INTERPRETATION AND CONCLUSIONS: These data suggest that adenoviral-mediated gene transfer could be feasible in myeloid leukemia cell lines and that it is inhibited by ATRA in differentiation-sensitive cells. The latter effect merits further investigation in order to verify whether this represents an ATRA-related or a differentiation-related phenomenon.