Targeting CDK6 and BCL2 exploits the "MYB Addiction" of Ph+ acute lymphoblastic leukemia
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ABSTRACT: 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.
ORGANISM(S): Homo sapiens
PROVIDER: GSE105826 | GEO | 2018/01/17
SECONDARY ACCESSION(S): PRJNA415464
REPOSITORIES: GEO
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