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Series GSE98380 Query DataSets for GSE98380
Status Public on Jul 31, 2018
Title Targeting the MTF2-MDM2 Axis Sensitizes Refractory Acute Myeloid Leukemia to Chemotherapy
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
Summary This SuperSeries is composed of the SubSeries listed below.

Deep sequencing has revealed that epigenetic modifiers are the most mutated genes in acute myeloid leukemia (AML). Thus, elucidating epigenetic dysregulation in AML is crucial to understand disease mechanisms. Here, we demonstrate that Metal Response Element Binding Transcription Factor 2/Polycomblike 2 (MTF2/PCL2) plays a fundamental role in the Polycomb repressive complex 2 (PRC2) and that its loss elicits an altered epigenetic state underlying refractory AML. Unbiased systems analyses identified the loss of MTF2-PRC2 repression of MDM2 as central to, and therefore a biomarker for, refractory AML. Thus, immature MTF2- deficient CD34+CD38- cells overexpress MDM2, thereby inhibiting p53 that leads to chemoresistance due to defects in cell cycle regulation and apoptosis. Targeting this dysregulated signaling pathway by MTF2 overexpression or MDM2 inhibitors sensitized refractory patient leukemic cells to induction chemotherapeutics and prevented relapse in AML patient-derived xenograft (PDX) mice. Therefore, we have uncovered a direct epigenetic mechanism by which MTF2 functions as a tumor suppressor required for AML chemotherapeutic sensitivity and identified a potential therapeutic strategy to treat refractory AML.
Overall design Refer to individual Series
Citation(s) 30115703
Submission date May 01, 2017
Last update date Jul 25, 2021
Contact name William Stanford
Phone 613-737-8899
Organization name Ottawa Hospital Research Institute
Lab Stanford
Street address 501 Smyth Road
City Ottawa
State/province Ontario
ZIP/Postal code K1H 8L6
Country Canada
Platforms (2)
GPL11154 Illumina HiSeq 2000 (Homo sapiens)
GPL18573 Illumina NextSeq 500 (Homo sapiens)
Samples (30)
GSM2592453 scramble control replicate 1
GSM2592454 MTF2 shRNA clone 3 replicate 1
GSM2592455 MTF2 shRNA clone 7 replicate 1
This SuperSeries is composed of the following SubSeries:
GSE98343 Targeting the MTF2-MDM2 Axis Sensitizes Refractory Acute Myeloid Leukemia to Chemotherapy [RNA-Seq]
GSE98378 Targeting the MTF2-MDM2 Axis Sensitizes Refractory Acute Myeloid Leukemia to Chemotherapy [ChIP-Seq]
BioProject PRJNA384954

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
GSE98380_RAW.tar 6.2 Gb (http)(custom) TAR (of BW)
SRA Run SelectorHelp

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