Silencing AML1-ETO gene expression leads to simultaneous activation of both pro-apoptotic and proliferation signaling

摘要: The t(8;21)(q22;q22) rearrangement represents the most common chromosomal translocation in acute myeloid leukemia (AML). It results a transcript encoding for fusion protein AML1-ETO (AE) with transcription factor activity. AE is considered to be an attractive target treating t(8;21) leukemia. However, expression alone insufficient cause transformation, and thus potential of such therapy remains unclear. Several genes are deregulated AML cells, including KIT that encodes tyrosine kinase receptor. Here, we show cells transduced short hairpin RNA vector targeting mRNAs have dramatic decrease growth rate caused by induction apoptosis deregulation cell cycle. A reduction mRNA levels was also observed AE-silenced but silencing reduced did not induce apoptosis. Transcription profiling escape death revealed activation number signaling pathways involved survival proliferation. In particular, find extracellular signal-regulated 2 (ERK2; known as mitogen-activated 1 (MAPK1)) could mediate 23 out 29 (79%) these upregulated may regarded key player establishing t(8;21)-positive leukemic resistant suppression.