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. Kok, D. B. Watkins, M. Biondo, S. J. Busfield, G. Vairo, K. Fuller, W. N. Erber, T. Sadras, R. Grose, D. T. Yeung, A. F. Lopez, D. K. Hiwase, T. P. Hughes, D. L. White

Research output: Contribution to journalArticle

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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 .

LanguageEnglish
Pages1263-1272
Number of pages10
JournalLeukemia
Volume30
Issue number6
DOIs
Publication statusPublished - 1 Jun 2016

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Cite this

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

In: Leukemia, Vol. 30, No. 6, 01.06.2016, p. 1263-1272.

Research output: Contribution to journalArticle

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AU - Nievergall, E.

AU - Reynolds, J.

AU - Kok, C. H.

AU - Watkins, D. B.

AU - Biondo, M.

AU - Busfield, S. J.

AU - Vairo, G.

AU - Fuller, K.

AU - Erber, W. N.

AU - Sadras, T.

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AU - Yeung, D. T.

AU - Lopez, A. F.

AU - Hiwase, D. K.

AU - Hughes, T. P.

AU - White, D. L.

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