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CD44-ligation induces, through ERK1/2 pathway, synthesis of cytokines TNF-α and IL-6 required for differentiation of THP-1 monoblastic leukemia cells

Leukemia volume 24, pages 1372–1375 (2010)Cite this article

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Acute monoblastic leukemia, also designated as AML5 subtype, is characterized by accumulation of monoblastic-like cells (AML5 blasts), which terminal differentiation is blocked. The AML5 subtype poorly responds to chemotherapy and still has bad prognosis. We have previously reported that CD44-ligation with specific monoclonal antibodies (mAbs) can reverse differentiation blockage in AML5 subtype,1 providing strong basis for the development, in AML5, of a CD44-targeted differentiation therapy that could be as efficient as that with retinoic acid in the promyelocytic AML subtype.

By monitoring differentiation using the gradual increase in expression of CD11b and CD14 monocytic-lineage antigens, we have recently shown that CD44-ligation triggers in AML5 blasts, a burst of cytokine synthesis, and that granulocyte-macrophage colony-stimulating factor(GM-CSF) and interleukin (IL)-8 are required to increase the expression of CD14.2 However, the mechanisms involved in CD44-induced differentiation, and especially in differentiating cytokine synthesis, are still unknown. Here, using the THP-1 monoblastic cell line as a model of AML5 blasts, and Hermes-3 anti-CD44 mAb (H3) to induce its differentiation, we show that CD44-ligation induces, through extracellular signal-regulated kinases (ERK)1/2 pathway, the synthesis of cytokines tumor necrosis factor (TNF)-α and IL-6 required for monocytic differentiation of these leukemic cells.

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Acknowledgements

This work was supported by grants from the National Institute for Health and Medical Research (INSERM), Denis-Diderot University Paris7, the Association for Cancer Research (ARC, grant N° 4956), Association Laurette Fugain (grant ALF08/06), the Canceropole (Grant R07089HH). SB and AS were supported by fellowships from ARC and the French Ministery for Research. We thank Aurore Gersenmeyer for her skilfull technician collaboration.

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  1. Inserm UMRS-940 Hematology - Immunology - Therapeutic Targets, Université Denis Diderot Paris-7, Saint-Louis Hospital, 1 avenue Claude Vellefaux, Paris, France

    S Bourcier, A Sansonetti, L Durand, C Chomienne, J Robert-Lézénés & F Smadja-Joffe

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  1. S Bourcier
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  2. A Sansonetti
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  3. L Durand
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Correspondence to F Smadja-Joffe.

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Bourcier, S., Sansonetti, A., Durand, L. et al. CD44-ligation induces, through ERK1/2 pathway, synthesis of cytokines TNF-α and IL-6 required for differentiation of THP-1 monoblastic leukemia cells. Leukemia 24, 1372–1375 (2010). https://doi.org/10.1038/leu.2010.100

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