Research output per year
Research output per year
Pablo Peña, Mia Eriksson, R Ramakrishnan, M Chapellier, Carl Högberg, C Orsmark-Pietras, J Richter, Anna Andersson, T Fioretos, M Järås
Research output: Contribution to journal › Article › peer-review
Cytokines provide signals that regulate immature normal and acute myeloid leukemia (AML) cells in the bone marrow microenvironment. We here identify interleukin 4 (IL4) as a selective inhibitor of AML cell growth and survival in a cytokine screen using fluorescently labeled AML cells. RNA-sequencing of the AML cells revealed an IL4-induced upregulation of Stat6 target genes and enrichment of apoptosis-related gene expression signatures. Consistent with these findings, we found that IL4 stimulation of AML cells induced Stat6 phosphorylation and that disruption of Stat6 using CRISPR/Cas9-genetic engineering rendered cells partially resistant to IL4-induced apoptosis. To evaluate whether IL4 inhibits AML cells in vivo, we expressed IL4 ectopically in AML cells transplanted into mice and also injected IL4 into leukemic mice; both strategies resulted in the suppression of the leukemia cell burden and increased survival. Notably, IL4 exposure caused reduced growth and survival of primary AML CD34(+)CD38(-) patient cells from several genetic subtypes of AML, whereas normal stem and progenitor cells were less affected. The IL4-induced apoptosis of AML cells was linked to Caspase-3 activation. Our results demonstrate that IL4 selectively induces apoptosis of AML cells in a Stat6-dependent manner, findings that may translate into new therapeutic opportunities in AML.Leukemia accepted article preview online, 18 August 2017. doi:10.1038/leu.2017.261.
Original language | English |
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Pages (from-to) | 588-596 |
Journal | Leukemia |
Volume | 32 |
Issue number | 3 |
Early online date | 2017 Aug 18 |
DOIs | |
Publication status | Published - 2018 |
Research output: Thesis › Doctoral Thesis (compilation)
Research output: Thesis › Doctoral Thesis (compilation)
Eriksson, M. (Research student), Järås, M. (Supervisor) & Fioretos, T. (Supervisor)
2014/03/03 → 2018/03/08
Project: Dissertation