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Series GSE79068 Query DataSets for GSE79068
Status Public on Mar 31, 2017
Title Interleukin 4 induces apoptosis of acute myeloid leukemia cells in a Stat6-dependent manner
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Acute myeloid leukemia (AML) is associated with poor prognosis, and there is a strong need to develop new therapeutic strategies to improve treatments. We performed a cytokine screen with 114 recombinant proteins to identify selective negative regulators of primitive murine AML cells relative to normal bone marrow cells. The top candidate identified was interleukin 4 (IL4), as it showed the most selective inhibition of leukemia cell growth. Stimulating leukemia cells ex vivo with IL4 and transplanting the cells into mice resulted in reduced leukemia burden and prolonged survival compared with controls. In contrast, IL4 did not inhibit the function of normal hematopoietic stem and progenitor cells in long-term bone marrow repopulation assays. Moreover, we found that IL4 treatment of leukemia cells induced Stat6 phosphorylation, and that leukemia cells with Stat6 knocked out using CRISPR/Cas9-genetic engineering were partially resistant to IL4 stimulation, revealing Stat6 as a critical mediator of the IL4 effect. To evaluate whether IL4 has in vivo therapeutic efficacy, we expressed IL4 ectopically in leukemia cells in vivo and also injected IL4 into leukemic mice; both strategies resulted in the suppression of the leukemia cell burden and increased survival. Further analysis revealed that IL4 treatment induces apoptosis in the leukemia cells. Importantly, IL4 exposure also inhibited the growth and survival of primary AML patient cells. In summary, these findings demonstrate that IL4 selectively inhibits AML cells in a Stat6-dependent manner, thus revealing IL4 as a candidate therapeutic agent in AML. IL4 (ProSpec, East Brunswick NJ, USA) was resuspended following the provider guidelines and stored in aliquotes at -80 °C. Mouse MLL-AF9 leukemia cells were provided by Dr. Benjamin Ebert (Brigham and Women’s Hospital, Boston MA, USA). The murine leukemia cells were cultured in SFEM (StemCell Tech) supplemented with 1% penicillin/streptomycin at 37 °C with 5% CO2.
Overall design Mouse MLL-AF9 leukemia cells were grown in 20 ng/mL IL3 with or without IL4 (100 ng/mL) for 18 hours.
Contributor(s) Peña-Martínez P
Citation(s) 28819278
Submission date Mar 10, 2016
Last update date May 15, 2019
Contact name Pablo Peña-Martínez
Organization name Lund University
Department Clinical Genetics
Street address Klinikgatan 28
City Lund
ZIP/Postal code 22184
Country Sweden
Platforms (1)
GPL19057 Illumina NextSeq 500 (Mus musculus)
Samples (14)
GSM2084856 Leukemia cells IL3 rep1
GSM2084857 Leukemia cells IL3 rep2
GSM2084858 Leukemia cells IL3 rep3
BioProject PRJNA314854
SRA SRP071580

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Supplementary file Size Download File type/resource
GSE79068_MLL_IL4_TMM.txt.gz 645.2 Kb (ftp)(http) TXT
GSE79068_NBM_IL4_TMM.txt.gz 555.7 Kb (ftp)(http) TXT
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Raw data are available in SRA
Processed data are available on Series record

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