BIOLOGICAL CONSEQUENCES OF P160(V-ABL) PROTEIN-TYROSINE KINASE-ACTIVITY IN A PRIMITIVE MULTIPOTENT HEMATOPOIETIC-CELL LINE

A temperature sensitive abl protein tyrosine kinase gene was transferr ed into a multipotent haemopoietic stem cell line, and the primary bio logical effects of expression of the gene were examined at the permiss ive and non-permissive temperatures. Unlike previous studies in factor -dependent cell lines, we found that expression of the functional abl protein tyrosine kinase did not lead to growth autonomy. Furthermore, the cells were still able to undergo terminal myeloid differentiation. However, expression of the functional gene did lead to a delay in mat uration with a concomitant increase in cell production, had a modest e ffect in terms of delayed apoptosis particularly when the cells were m aintained at a high cell density, and slightly increased the response to sub-optimal concentrations of IL-3. In many respects, therefore, th e effects of abl protein tyrosine kinase in these cells mimics the eff ect of bcr/abl in primary haemopoietic cells where growth factor indep endence and an aberrant differentiation profile are relatively late ev ents in clonal evoluation and are not intermediate consequences of act ivation of the abl gene.