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Series GSE105826 Query DataSets for GSE105826
Status Public on Jan 17, 2018
Title Targeting CDK6 and BCL2 exploits the "MYB Addiction" of Ph+ acute lymphoblastic leukemia
Organism Homo sapiens
Experiment type Expression profiling by array
Summary 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.
 
Contributor(s) De Dominici M, Porazzi P, Soliera AR, Mariani SA, Addya S, Fortina P, Peterson LF, Spinelli O, Rambaldi A, Martinelli G, Ferrari A, Iacobucci I, Calabretta B
Citation(s) 29233926
NIH grant(s)
Grant ID Grant title Affiliation Name
R01 CA167169 Targeting the C/EBPalpha-Gfi-pathway in CML stem cells THOMAS JEFFERSON UNIVERSITY BRUNO CALABRETTA
Submission date Oct 23, 2017
Last update date Feb 01, 2019
Contact name Marco De Dominici
E-mail(s) marco.dedominici@jefferson.edu
Phone 2155034523
Organization name Thomas Jefferson University
Department Cancer Biology
Lab Calabretta
Street address 10th
City Philadelphia
State/province Pennsylvania
ZIP/Postal code 19107
Country USA
 
Platforms (2)
GPL6244 [HuGene-1_0-st] Affymetrix Human Gene 1.0 ST Array [transcript (gene) version]
GPL23159 [Clariom_S_Human] Affymetrix Clariom S Assay, Human (Includes Pico Assay)
Samples (12)
GSM2828468 BV173 untreated 1
GSM2828469 BV173 untreated 2
GSM2828470 BV173 untreated 3
Relations
BioProject PRJNA415464

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE105826_RAW.tar 32.3 Mb (http)(custom) TAR (of CEL, CHP)
Processed data included within Sample table
Processed data provided as supplementary file

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