The Leukemia-associated ETO homologues are differently expressed during hematopoietic differentiation.

ABSTRACT

The Eight twenty-one (ETO) homologues are nuclear repressor proteins including ETO, myeloid-transforming gene-related protein 1 (MTGR1), and myeloid-transforming gene chromosome 16 (MTG16). ETO and MTG16 are both part of fusion proteins resulting from chromosomal translocations associated with acute myeloid leukemia. Expression of these chimeras results in a differentiation block that contributes to the onset of leukemia. In order to elucidate the relation between the ETO homologues and hematopoietic differentiation, we determined the expression of the homologues during differentiation of leukemic and normal hematopoietic cells. Our results showed MTGR1 and MTG16 to be ubiquitously expressed in leukemic cell lines, whereas expression of ETO was observed only in an erythroleukemic cell line. The MTGR1 and MTG16 proteins decreased during all trans-retinoic acid-, but not vitamin D(3)-induced differentiation of leukemic cells. The reduction seemed to reflect a decrease in transcript levels as well as in protein stability. MTGR1 transcripts were ubiquitously expressed in human bone marrow cells. The MTG16 transcripts of CD34(+) progenitor cells were rapidly downregulated by cytokine-induced differentiation into myeloid or erythroid lineages. ETO transcripts, present at very low abundance in CD34(+) progenitor cells, were transiently upregulated during erythroid differentiation. In conclusion, the differential expression of the ETO homologues suggests that they may have a potential role in hematopoietic differentiation.