c-Myc Interferes with the Commitment to Differentiation of Murine Erythroleukemia Cells at a Reversible Point

When murine erythroleukemia (MEL) cells, containing the transferred rat c-myc gene under the control of human metallothionein II gene promoter, are induced to differentiate with dimethyl sulfoxide, the level of differentiation is dependent on the c-Myc level, which is modulated by the addition of Zn ions. In this work, we examined the point of inhibition of differentiation by elevated levels of c-Myc in one (clone 38-2) of the typical transformants. Commitment assay indicated that elevated levels of c-Myc interfere with entry of the transformant into the commitment event, but when c-myc expression was reduced by removing Zn ions from the medium, the cells could reenter the commitment program. However, once the cells were committed, such cells could not return to the uncommitted state. In addition, time-dependent expression of two erythroid specific genes was inhibited by elevated levels of c-Myc in time-dependent manner. These results suggest that c-Myc modulates MEL cell differentiation at a reversible point of commitment.