Reversibility of differentiation and proliferative capacity in avian myelomonocytic cells transformed by tsE26 leukemia virus.

Chicken hematopoietic cells infected with E26 leukemia virus can be transformed into growth factor-dependent, rapidly proliferating cells that exhibit properties of immature myelomonocytic cells. Cells infected with a mutant of E26 that carries a temperature-sensitive lesion, presumably residing in the myb oncogene, differentiate into resting, macrophage-like cells when shifted from 37 degrees to 42 degrees C (Beug et al. 1984). Here we show that differentiated tsE26 cells gradually reacquire an immature phenotype and proliferative capacity when shifted back to 37 degrees C, provided that they are kept at 42 degrees C no longer than 4-8 days. We also show that DNA synthesis inhibitors do not prevent terminal differentiation at 42 degrees C but inhibit the complete reexpression of the immature phenotype in downshift experiments. Our results suggest that the reactivation of the E26 protein function can both induce a "retro-differentiation" and cell proliferation in myelomonocytic target cells.