To identify vectors that provide optimal gene expression in human hema
topoietic cells, we investigated retroviruses containing the adenosine
deaminase (ADA) gene under the transcriptional control of the promote
rs/enhancers of Moloney murine leukemia virus and the human cytomegalo
virus (CMV) immediate-early gene, ADA expression was monitored in tran
sduced human multipotential promyelocytic leukemic HL-60 cells and hum
an monocytic leukemic THP-1 cells, HL-60 cells can be induced by phorb
ol ester to differentiate into macrophage lineage cells and by retinoi
c acid into granulocytic cells, THP-1 cells undergo phorbol ester-indu
ced differentiation to macrophage cells, In LNCA-transduced HL-60 deri
ved macrophage cells, ADA controlled by the CMV promoter was expressed
at 100.0 mu mol/hr . mg, in contrast to 1.2 mu mol/hr . mg from LN-tr
ansduced control cells, LNCA-transduced THP-1 macrophage cells showed
a similar increase in ADA activity over control cells, These elevated
enzyme activities were confirmed by Northern blots, which showed subst
antial increases in ADA mRNA derived from the CMV promoter, This sugge
sts use of the CMV promoter for gene therapy targeted at macrophages,
as, for example, in the treatment of lysosomal storage disorders such
as Gaucher disease, These inducible cell lines have allowed the evalua
tion of transduced gene expression in proliferating and differentiatin
g hematopoietic cells that may serve as an in vitro model of bone marr
ow-targeted gene therapy.