The browser you are using is not supported by this website. All versions of Internet Explorer are no longer supported, either by us or Microsoft (read more here: https://www.microsoft.com/en-us/microsoft-365/windows/end-of-ie-support).

Please use a modern browser to fully experience our website, such as the newest versions of Edge, Chrome, Firefox or Safari etc.

Thoas Fioretos

Thoas Fioretos

Research team manager

Thoas Fioretos

Interleukin 4 induces apoptosis of acute myeloid leukemia cells in a Stat6 dependent manner

Author

  • Pablo Peña
  • Mia Eriksson
  • R Ramakrishnan
  • M Chapellier
  • Carl Högberg
  • C Orsmark-Pietras
  • J Richter
  • Anna Andersson
  • T Fioretos
  • M Järås

Summary, in English

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.

Department/s

  • Division of Clinical Genetics
  • Translational Genomic and Functional Studies of Leukemia
  • Division of Molecular Medicine and Gene Therapy
  • BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation
  • StemTherapy: National Initiative on Stem Cells for Regenerative Therapy

Publishing year

2018

Language

English

Pages

588-596

Publication/Series

Leukemia

Volume

32

Issue

3

Document type

Journal article

Publisher

Nature Publishing Group

Topic

  • Cell and Molecular Biology

Keywords

  • Journal Article

Status

Published

Project

  • Identification and characterization of candidate therapeutic targets in acute myeloid leukemia

Research group

  • Translational Genomic and Functional Studies of Leukemia

ISBN/ISSN/Other

  • ISSN: 1476-5551