Establishment of a pluripotent preleukaemic stem cell line by expression of the AML1-ETO fusion protein in Notch1-immortalized HSCN1cl10 cells

The AML1-ETO fusion has been associated with up to 40% of acute myeloid leukaemia French-American-British classified M2 cases. This chimaeric protein interferes with normal AML1 function and disrupts critical transcriptional regulation of haematopoiesis. Current evidence suggests that AML1-ETO alone is insufficient to induce leukaemia, but rather is a co-operating event in leukaemogenesis. We developed a pluripotent murine haematopoietic stem cell line expressing the AML1-ETO fusion protein that displays in vitro and in vivo properties consistent with a preleukaemic state, including inhibition of terminal granulocytic differentiation in vitro and the development of non-lymphoid leukaemias in vivo. This cell line represents a potential platform for the introduction and in vitro rapid screening of candidate genes thought to co-operate with AML1-ETO in developing frank leukaemia.