Analysis of Target Genes of Leukemia-associated Chimeric Transcription Factors AML1-MTG8 and FUS-ERG

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Chromosomal translocations found in human leukemias frequently involve genes that encode transcription factors, and result in the production of chimeric transcription factors. These chimeric transcription factors are thought to dysregulate the expression of genes which are crucial for normal cell differentiation and proliferation. However, which genes are dysregulated by such transcription factors and responsible for leukemogenesis is largely unknown. To elucidate the role in leukemogenesis of the chimeric transcription factors AML1-MTG8 and FUS-ERG, which are produced by t(8;21) and t(16;21) translocations in acute myeloid leukemia, we have been investigating the genes under the downstream control of thesetranscription factors using a microarray-based expression analysis. We found that AML1-MTG8 up-regulates expression of the G-CSF receptor and TIS11b genes and FUS-ERG also up-regulates expression of G-CSF receptor. Enhanced expression of G-CSF receptor and TIS11b results in stimulation of G-CSF-dependent growth. It was also revealed that AML1-MTG8 up-regulates azurophil granule protein genes, and induce partial granulocytic differentiation of myeloid cells.