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Human neutrophil elastase is not a target for therapy in chronic myeloid leukaemia

Leukemia volume 20, pages 2054–2055 (2006)Cite this article

The primary granule protein (PGP), human neutrophil elastase (HNE), is often associated with inflammatory-type reactions but also has a role in granulopoiesis.1 PGP proteases, including HNE, normally provide negative feedback of granulopoiesis by controlling the availability of granulocyte colony-stimulating factor (G-CSF) proportionate to the relative abundance of mature granulocytes that are greatly elevated in number as a clinical feature of chronic myeloid leukaemia (CML).

HNE added to normal CD34+ stem cells in culture blocks granulocyte macrophage (GM) colony formation and induces apoptosis.1, 2 The G-CSF receptor is not digested; instead HNE targets G-CSF protein exerting a negative feedback on cytokine activity.1 High plasma levels of HNE2 and low G-CSF3 have been reported in CML. Moreover, it is known that Ph+ cells can invoke autocrine G-CSF cytokine production.4 Taken together, these data suggest that HNE may contribute to the CML phenotype of Ph+ clonal dominance as Ph− normal cells die without growth factors.

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References

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Acknowledgements

We gratefully acknowledge the staff of Glasgow Royal Infirmary Wards 40/41/42 for sample procurement. The Kay Kendall Leukaemia Fund (HGJ), Scottish National Blood Transfusion Service (EKA) and Leukaemia Research Fund (TLH) supported this work.

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Authors and Affiliations

  1. Division of Cancer Sciences and Molecular Pathology, Section of Experimental Haematology, University of Glasgow, Glasgow, UK

    E K Allan, T L Holyoake & H G Jørgensen

  2. Scottish National Blood Transfusion Service, Glasgow Royal Infirmary, Glasgow, UK

    E K Allan

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  1. E K Allan
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  2. T L Holyoake
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  3. H G Jørgensen
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Allan, E., Holyoake, T. & Jørgensen, H. Human neutrophil elastase is not a target for therapy in chronic myeloid leukaemia. Leukemia 20, 2054–2055 (2006). https://doi.org/10.1038/sj.leu.2404411

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