Block of granulocytic differentiation of 32Dcl3 cells by AML1/ETO(MTG8) but not by highly expressed Bcl-2

The chimeric gene, AML1/ETO (MTG8), generated in t(8;21) acute myeloid leuk emia enhances the expression of Bcl-2. To evaluate whether this enhancement is the primary role of AML1/ETO in leukemogenesis, effects of over-express ion of Bcl-2 in the murine myeloid precursor cell line, 32Dc13, were examin ed. When 32Dc13 cells expressing exogenous Bcl-2 were induced to differenti ate, the onset of morphological differentiation,vas delayed. However, even the cells expressing very high levels of exogenous Bcl-2 eventually underwe nt differentiation without a significant decrease in the synthesis of Bcl-2 . On the contrary, 32Dc13 cells stably expressing AML1/ETO mere completely resistant to differentiation and continued to grow in the presence of G-CSF . These results are consistent with the interpretation that stimulation of Bcl-2 expression is not the primary target of AML1/ETO.