Examples: histone, BN000065

Project: PRJNA415464

Transcriptome analysis of two Ph+ acute lymphoblastic leukemia cell lines after doxycycline induced silencing of MYB. Current treatment options for Ph+ acute lymphoblastic leukemia (ALL) do not result in long term remission. MYB transcription factor has been shown to be selectively important for Ph+ ALL cell survival and proliferation however the mechanisms for this oncogene addiction are poorly understood and no bona-fide MYB inhibitors currently exist. To overcome these limitations, we analyzed the transcriptome of MYB silenced Ph+ ALL in search for genes regulated by MYB that could serve as potential pharmacological targets. We observed that among MYB-regulated genes, those involved in cell cycle regulation are significantly over-represented. We found that CDK6 and BCL2 are MYB targets pivotal for MYB dependent regulation of proliferation and survival respectively. Furthermore, their inhibition suppresses leukemia growth in vitro and in vivo thus providing a potential treatment approach for patients that fails or do not respond to conventional treatments. Overall design: Ph+ ALL cells BV173 and SUP-B15 were transduced with the lentiviral vector pLVTSH expressing a MYB-targeting shRNA in a doxycycline inducible manner. Cells were left untreated or treated with doxycycline for 24 h. Then, RNA was extracted from three independent untreated and three doxycycline treated samples and analyzed by microarray.

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