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Chronic myelogenous leukemia

TGF-α and IL-6 plasma levels selectively identify CML patients who fail to achieve an early molecular response or progress in the first year of therapy

Leukemia volume 30, pages 1263–1272 (2016)Cite this article

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Abstract

Early molecular response (EMR, BCR-ABL1 (IS)⩽10% at 3 months) is a strong predictor of outcome in imatinib-treated chronic phase chronic myeloid leukemia (CP-CML) patients, but for patients who transform early, 3 months may be too late for effective therapeutic intervention. Here, we employed multiplex cytokine profiling of plasma samples to test newly diagnosed CP-CML patients who subsequently received imatinib treatment. A wide range of pro-inflammatory and angiogenesis-promoting cytokines, chemokines and growth factors were elevated in the plasma of CML patients compared with that of healthy donors. Most of these normalized after tyrosine kinase inhibitor treatment while others remained high in remission samples. Importantly, we identified TGF-α and IL-6 as novel biomarkers with high diagnostic plasma levels strongly predictive of subsequent failure to achieve EMR and deep molecular response, as well as transformation to blast crisis and event-free survival. Interestingly, high TGF-α alone can also delineate a poor response group raising the possibility of a pathogenic role. This suggests that the incorporation of these simple measurements to the diagnostic work-up of CP-CML patients may enable therapy intensity to be individualized early according to the cytokine-risk profile of the patient.

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Acknowledgements

We thank Verity Saunders, Jarrad Goyne, Amity Frede and Jenny McLean for excellent technical assistance with patient sample processing and Bob Mirzai for excellent technical help with TGF-α immunocytochemistry. This study was supported by an NH&MRC Project Grant.

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Author notes

  1. T P Hughes and D L White: Joint senior authors.

Authors and Affiliations

  1. Cancer Theme, South Australian Health and Medical Research Institute (SAHMRI), Adelaide, SA, Australia

    E Nievergall, C H Kok, D B Watkins, T Sadras, R Grose, T P Hughes & D L White

  2. School of Medicine, University of Adelaide, Adelaide, SA, Australia

    E Nievergall, C H Kok, D B Watkins, T Sadras, D T Yeung, D K Hiwase, T P Hughes & D L White

  3. Biostatistics Platform, Faculty of Medicine, Nursing and Health Sciences, Monash University, The Alfred Centre, Melbourne, VIC, Australia

    J Reynolds

  4. CSL Limited, Parkville, VIC, Australia

    M Biondo, S J Busfield & G Vairo

  5. School of Pathology and Laboratory Medicine, The University of Western Australia, Perth, WA, Australia

    K Fuller & W N Erber

  6. Department of Haematology, SA Pathology, Adelaide, SA, Australia

    D T Yeung, D K Hiwase & T P Hughes

  7. Centre for Cancer Biology, SA Pathology and UniSA, Adelaide, SA, Australia

    D T Yeung, A F Lopez & T P Hughes

  8. Discipline of Paediatrics, University of Adelaide, Adelaide, SA, Australia

    D L White

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  1. E Nievergall
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Correspondence to D L White.

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Competing interests

JR is a Novartis Shareholder. DTY and TPH receive honoraria and research funding from Novartis Oncology, Bristol-Myers Squibb and Ariad. DLW receives research funding from Novartis Oncology, Bristol-Myers Squibb and Ariad. MB and GV are employed by CSL Limited, and SJB was employed by CSL Limited. EN, CHK, DBW, KF, WNE, TS, RG, AFL and DKH declare no conflict of interest.

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Nievergall, E., Reynolds, J., Kok, C. et al. TGF-α and IL-6 plasma levels selectively identify CML patients who fail to achieve an early molecular response or progress in the first year of therapy. Leukemia 30, 1263–1272 (2016). https://doi.org/10.1038/leu.2016.34

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