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

E. Nievergall, J. Reynolds, C.H. H. Kok, D.B. B. Watkins, M. Biondo, S.J J Busfield, G. Vairo, Kathy A. Fuller, Wendy N. Erber, T. Sadras, R. Grose, D.T. T. Yeung, A.F. F. Lopez, D.K. K. Hiwase, T.P. P. Hughes, D.L. L. White

    Research output: Contribution to journalArticle

    13 Citations (Scopus)

    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 . © 2016 Macmillan Publishers Limited.
    Original languageEnglish
    Pages (from-to)1263-1272
    Number of pages10
    JournalLeukemia
    Volume30
    Issue number6
    DOIs
    Publication statusPublished - 2016

    Fingerprint

    Interleukin-6
    Leukemia, Myeloid, Chronic Phase
    Cytokines
    Therapeutics
    Blast Crisis
    Chemokines
    Protein-Tyrosine Kinases
    Disease-Free Survival
    Intercellular Signaling Peptides and Proteins
    Biomarkers
    Tissue Donors
    Imatinib Mesylate

    Cite this

    Nievergall, E., Reynolds, J., Kok, C. H. H., Watkins, D. B. B., Biondo, M., Busfield, S. J. J., ... White, D. L. L. (2016). 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(6), 1263-1272. https://doi.org/10.1038/leu.2016.34
    Nievergall, E. ; Reynolds, J. ; Kok, C.H. H. ; Watkins, D.B. B. ; Biondo, M. ; Busfield, S.J J ; Vairo, G. ; Fuller, Kathy A. ; Erber, Wendy N. ; Sadras, T. ; Grose, R. ; Yeung, D.T. T. ; Lopez, A.F. F. ; Hiwase, D.K. K. ; Hughes, T.P. P. ; White, D.L. L. / 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. In: Leukemia. 2016 ; Vol. 30, No. 6. pp. 1263-1272.
    @article{7e3010dc7b8f44d081ce3164a30e8296,
    title = "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",
    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 . {\circledC} 2016 Macmillan Publishers Limited.",
    author = "E. Nievergall and J. Reynolds and Kok, {C.H. H.} and Watkins, {D.B. B.} and M. Biondo and Busfield, {S.J J} and G. Vairo and Fuller, {Kathy A.} and Erber, {Wendy N.} and T. Sadras and R. Grose and Yeung, {D.T. T.} and Lopez, {A.F. F.} and Hiwase, {D.K. K.} and Hughes, {T.P. P.} and White, {D.L. L.}",
    year = "2016",
    doi = "10.1038/leu.2016.34",
    language = "English",
    volume = "30",
    pages = "1263--1272",
    journal = "Leukemia",
    issn = "0887-6924",
    publisher = "Nature Publishing Group",
    number = "6",

    }

    Nievergall, E, Reynolds, J, Kok, CHH, Watkins, DBB, Biondo, M, Busfield, SJJ, Vairo, G, Fuller, KA, Erber, WN, Sadras, T, Grose, R, Yeung, DTT, Lopez, AFF, Hiwase, DKK, Hughes, TPP & White, DLL 2016, '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, vol. 30, no. 6, pp. 1263-1272. https://doi.org/10.1038/leu.2016.34

    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. / Nievergall, E.; Reynolds, J.; Kok, C.H. H.; Watkins, D.B. B.; Biondo, M.; Busfield, S.J J; Vairo, G.; Fuller, Kathy A.; Erber, Wendy N.; Sadras, T.; Grose, R.; Yeung, D.T. T.; Lopez, A.F. F.; Hiwase, D.K. K.; Hughes, T.P. P.; White, D.L. L.

    In: Leukemia, Vol. 30, No. 6, 2016, p. 1263-1272.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - 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

    AU - Nievergall, E.

    AU - Reynolds, J.

    AU - Kok, C.H. H.

    AU - Watkins, D.B. B.

    AU - Biondo, M.

    AU - Busfield, S.J J

    AU - Vairo, G.

    AU - Fuller, Kathy A.

    AU - Erber, Wendy N.

    AU - Sadras, T.

    AU - Grose, R.

    AU - Yeung, D.T. T.

    AU - Lopez, A.F. F.

    AU - Hiwase, D.K. K.

    AU - Hughes, T.P. P.

    AU - White, D.L. L.

    PY - 2016

    Y1 - 2016

    N2 - 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 . © 2016 Macmillan Publishers Limited.

    AB - 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 . © 2016 Macmillan Publishers Limited.

    U2 - 10.1038/leu.2016.34

    DO - 10.1038/leu.2016.34

    M3 - Article

    VL - 30

    SP - 1263

    EP - 1272

    JO - Leukemia

    JF - Leukemia

    SN - 0887-6924

    IS - 6

    ER -