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Series GSE184015 Query DataSets for GSE184015
Status Public on Sep 15, 2021
Title Targeting miR-126 in inv(16) acute myeloid leukemia inhibits leukemia development and leukemia stem cell maintenance
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Acute myeloid leukemia (AML) harboring inv(16)(p13q22) expresses high levels of miR-126. Here we show that the CBFB-MYH11 (CM) fusion gene upregulates miR-126 expression through aberrant miR-126 transcription and perturbed miR-126 biogenesis via the HDAC8/RAN-XPO5-RCC1 axis. Aberrant miR-126 upregulation promotes survival of leukemia-initiating progenitors and is critical for initiating and maintaining CM-driven AML. We show that miR-126 enhances MYC activity through the SPRED1/PLK2-ERK-MYC axis. Notably, genetic deletion of miR-126 significantly reduced AML rate and extended survival in CM knock-in mice. Therapeutic depletion of miR-126 with an anti-miR-126 (miRisten) inhibited AML cell survival, reduced leukemia burden and leukemia stem cell (LSC) activity in inv(16) AML murine and xenograft models. Combination of miRisten with chemotherapy further enhanced the anti-leukemia and anti-LSC activity. Overall, this study provides molecular insights for the mechanism and impact of miR-126 dysregulation in leukemogenesis and highlights the potential of miR-126 depletion as a new therapeutic approach for inv(16) AML.
 
Overall design Total 10 LSK samples were analyzed in this study. 5 samples as CM, 5 samples as CM/miR-126Δ/Δ
 
Contributor(s) Zhang L, Wu D, Li M, Li S, Chen W
Citation(s) 34686664
Submission date Sep 13, 2021
Last update date Dec 02, 2021
Contact name WEI CHEN
E-mail(s) weichen2@coh.org
Organization name City of Hope National Medical Center
Department Integrative Genomics Core
Street address 655 e huntington dr
City monrovia
State/province CA
ZIP/Postal code 91016
Country USA
 
Platforms (1)
GPL17021 Illumina HiSeq 2500 (Mus musculus)
Samples (10)
GSM5575912 CM/miR-126Δ/Δ-1
GSM5575913 CM/miR-126Δ/Δ-2
GSM5575914 CM/miR-126Δ/Δ-3
Relations
BioProject PRJNA762718
SRA SRP336810

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SOFT formatted family file(s) SOFTHelp
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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE184015_new.RPKM_ykuo_200702_GEO.txt.gz 1.6 Mb (ftp)(http) TXT
GSE184015_new.counts_ykuo_200702_GEO.txt.gz 770.5 Kb (ftp)(http) TXT
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Processed data are available on Series record

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