C-ERBA-ALPHA/T3R AND RARS CONTROL COMMITMENT OF HEMATOPOIETIC SELF-RENEWING PROGENITOR CELLS TO APOPTOSIS OR DIFFERENTIATION AND ARE ANTAGONIZED BY THE V-ERBA ONCOGENE

In AEV-transformed erythroleukemic cells the v-erbA gene product is likely to antagonize the function of triiodothyronine (T3) and retinoic acid (RA) receptors and thereby to block cell differentiation. We have thus investigated the effects of T3 and RA on normal early erythrocytic progenitor cells. Here we show: (1) that either RA or T3 play an essential role during the early commitment to erythrocytic differentiation, (2) that both T3 and RA induce death by apoptosis and a strong inhibition of self-renewal in progenitor cells grown in the absence of differentiation-inducing agents and (3) that the v-erbA oncogene renders erythrocytic progenitor cells insensitive to apoptosis and to self-renewal inhibition induced by RA or T3. The behaviour of a nontransforming mutant of v-evbA suggests that this v-erbA-induced protection is related to its transforming potential.