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Series GSE89778 Query DataSets for GSE89778
Status Public on Nov 14, 2016
Title Pluripotent Reprogramming of Human AML Resets Leukemic Behavior and Models Therapeutic Targeting of Subclones
Organism Homo sapiens
Experiment type Methylation profiling by array
Expression profiling by high throughput sequencing
Summary Understanding the contribution of abnormal genetic and epigenetic programs to acute myeloid leukemia (AML) is necessary for the integrated design of targeted therapies. To investigate this, we determined the effect of epigenetic reprogramming on leukemic behavior by generating induced pluripotent stem cells (iPSCs) from AML patient samples harboring MLL rearrangements. AML-derived iPSCs (AML-iPSCs) retained leukemic mutations, but reset leukemic DNA methylation/gene expression patterns and lacked leukemic potential. However, when differentiated into hematopoietic cells, AML-iPSCs reacquired the ability to give rise to leukemia in vivo and reestablished leukemic methylation/gene expression patterns, including an aberrant MLL signature, indicating that epigenetic reprogramming was insufficient to eliminate leukemic behavior. In one case, we identified distinct AML-iPSC KRAS mutant and wildtype subclones that demonstrated differential growth properties and therapeutic susceptibilities, predicting KRAS wildtype clonal relapse due to increased cytarabine resistance. Increased cytarabine resistance was further observed in a cohort of KRAS wildtype MLL-rearranged AML samples, demonstrating the utility of AML-iPSCs in predicting subclonal relapse and facilitating clonal targeting in AML.

This SuperSeries is composed of the SubSeries listed below.
 
Overall design Refer to individual Series
 
Citation(s) 28089908
Submission date Nov 10, 2016
Last update date Jul 25, 2021
Contact name Andrew Gentles
Organization name Stanford University
Street address 1201 Welch Road
City Stanford
State/province CA
ZIP/Postal code 94305
Country USA
 
Platforms (2)
GPL13534 Illumina HumanMethylation450 BeadChip (HumanMethylation450_15017482)
GPL20301 Illumina HiSeq 4000 (Homo sapiens)
Samples (87)
GSM2388511 #1-SU042 AML
GSM2388512 #2-SU223 AML
GSM2388513 #3-SU042 AML Ms3
This SuperSeries is composed of the following SubSeries:
GSE89776 Pluripotent Reprogramming of Human AML Resets Leukemic Behavior and Models Therapeutic Targeting of Subclones [methylation]
GSE89777 Pluripotent Reprogramming of Human AML Resets Leukemic Behavior and Models Therapeutic Targeting of Subclones [RNA-seq]
Relations
BioProject PRJNA353502

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
GSE89778_RAW.tar 568.1 Mb (http)(custom) TAR (of IDAT)
SRA Run SelectorHelp

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