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Interleukin-4 stimulates proliferation and growth of T-cell acute lymphoblastic leukemia cells by activating mTOR signaling

Leukemia volume 23, pages 206–208 (2009)Cite this article

Interleukin-4 (IL-4) is produced within the bone marrow (BM) microenvironment either by nonresident circulating cells, namely T lymphocytes, mast cells, and basophils or by BM stromal cells. Importantly, IL-4 is able to induce proliferation of T-cell acute lymphoblastic leukemia (T-ALL) cells.1 Therefore, IL-4 produced in the BM milieu might influence the progression of T-ALL by stimulating proliferation of tumor cells. However, the exact mechanisms by which IL-4 induces leukemia expansion remain unknown.

The effects of IL-4 on normal lymphocytes involve at least two signaling pathways, Jak/STAT and PI3K/Akt(PKB).2 In addition, IL-4 activates the PI3K downstream target mTOR, which regulates cell cycle completion in activated mature T-cells.3 Constitutive activation of mTOR has been reported in some T-ALL cases4 and suggested to regulate viability, cell size and proliferation of tumor cells. However, leukemia cells depend not only on constitutive, cell-autonomous mechanisms but also on cues from the microenvironment to fully activate key signaling molecules that are essential for tumor expansion and decreased sensitivity to chemotherapy.5, 6 Therefore, we investigated whether mTOR is involved in IL-4-mediated proliferation and growth of T-ALL cells.

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Acknowledgements

This study was supported by FCT PPCDT/SAU-OBS/58913 (JTB), SAU/13240 and CBO/34914 (AAC), and NIH RO1-CA104596 and RO1-AI43552 (VAB) grants. BAC and LRM have FCT-SFRH PhD and BI fellowships, respectively.

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Author notes

  1. B A Cardoso, L R Martins, C I Santos and A A Cardoso: These authors contributed equally to this work.

Authors and Affiliations

  1. Cancer Biology Unit, Instituto de Medicina Molecular, Lisbon University Medical School, Lisbon, Portugal

    B A Cardoso, L R Martins, C I Santos & J T Barata

  2. Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard University Medical School, Boston, MA, USA

    L M Nadler & A A Cardoso

  3. Department of Hematology-Oncology and Cancer Biology, Beth Israel Deaconess Medical Center, Harvard University Medical School, Boston, MA, USA

    V A Boussiotis

  4. Department of Medicine, Indiana University Simon Cancer Center, Indiana University School of Medicine, Indianapolis, IN, USA

    A A Cardoso

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  1. B A Cardoso
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  2. L R Martins
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  7. J T Barata
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Correspondence to J T Barata.

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Supplementary Information accompanies the paper on the Leukemia website (http://www.nature.com/leu)

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Cardoso, B., Martins, L., Santos, C. et al. Interleukin-4 stimulates proliferation and growth of T-cell acute lymphoblastic leukemia cells by activating mTOR signaling. Leukemia 23, 206–208 (2009). https://doi.org/10.1038/leu.2008.178

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