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Contribution of GM-CSF and IL-8 to the CD44-induced differentiation of acute monoblastic leukemia

Leukemia volume 22, pages 873–876 (2008)Cite this article

Acute monoblastic leukemia is characterized by a monocytic differentiation blockage, resulting in the accumulation of immature monoblastic-like cells in bone marrow and circulating blood. Also designated as AML5, this acute myeloid leukemia (AML) subtype, which accounts for about 20% of adult AML cases, poorly responds to chemotherapy, and its association with hyperleukocytosis, extramedullary involvement and coagulation abnormalities contributes to its bad prognosis. AML5 blasts display high levels of the CD44 antigen, a highly glycosylated transmembrane adhesion molecule that is the main cellular receptor of hyaluronic acid. CD44 is also a signalling receptor involved in many cellular functions, including myeloid differentiation.1 We have previously shown that specific function-activating monoclonal antibodies (mAbs) to CD44 are capable of triggering the differentiation of AML5 blasts towards monocytic lineage.2 This differentiation was evidenced by the expression of lineage antigens (CD11b and CD14), the ability to produce oxidative bursts and cytological modifications, all specific to differentiated monocytes.2 These results have led us to develop a CD44-targeted differentiation therapy that could be as efficient in AML5 as the retinoic acid-based differentiation therapy in the promyelocytic AML subtype. However, a comprehensive development of this CD44-targeted therapy of AML5 requires to better understand the mechanisms sustaining the CD44-induced differentiation process.

It is now well established that an important function of CD44 in normal macrophages (when ligated with hyaluronic acid or with specific mAbs) is to induce the synthesis of cytokines (interleukin (IL)-1β, IL-6, IL-12, tumor necrosis factor, granulocyte–macrophage colony-stimulating factor (GM-CSF) and macrophage colony-stimulating factor (M-CSF)) and chemokines (IL-8, macrophage inflammatory protein (MIP)-1α and MIP-1β).3, 4 Interestingly, some of these cytokines and chemokines are involved in the monocytic differentiation of normal hematopoietic progenitors (IL-1β, IL-6, GM-CSF, M-CSF and IL-8) and, even more, can induce the differentiation of some leukemic cells (IL-1, IL-6, GM-CSF and G-CSF).5 These considerations prompted us to ask whether CD44 ligation triggers in AML5 blasts the synthesis of cytokines and chemokines contributing to their differentiation.

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Acknowledgements

This work was supported by grants from The Leukemia Lymphoma Society, ARC (Association for Cancer Research), La Fondation de France, Le Cancérôpole Ile de France and ANVAR (National Association for Research Valorisation; partnership with MATBiopharma, Evry, France). We acknowledge V Lancereaux for technical assistance and Dr Q Zhai for critical comments on the manuscript.

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  1. Inserm U718, Hôpital Saint-Louis, Paris, France

    J Delaunay, N Lecomte, S Bourcier, J Qi, Z Gadhoum, L Durand, C Chomienne, J Robert-Lézénès & F Smadja-Joffe

  2. MAT Biopharma, Evry, France

    N Lecomte

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Correspondence to F Smadja-Joffe.

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Delaunay, J., Lecomte, N., Bourcier, S. et al. Contribution of GM-CSF and IL-8 to the CD44-induced differentiation of acute monoblastic leukemia. Leukemia 22, 873–876 (2008). https://doi.org/10.1038/sj.leu.2404976

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