Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/103608
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Type: Journal article
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
Other Titles: TGF-alpha 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
Author: Nievergall, E.
Reynolds, J.
Kok, C.
Watkins, D.
Biondo, M.
Busfield, S.
Vairo, G.
Fuller, K.
Erber, W.
Sadras, T.
Grose, R.
Yeung, D.
Lopez, A.
Hiwase, D.
Hughes, T.
White, D.
Citation: Leukemia, 2016; 30(6):1263-1272
Publisher: Nature Publishing Group
Issue Date: 2016
ISSN: 0887-6924
1476-5551
Statement of
Responsibility: 
E Nievergall, J Reynolds, CH Kok, DB Watkins, M Biondo, SJ Busfield, G Vairo, K Fuller, WN Erber, T Sadras, R Grose, DT Yeung, AF Lopez, DK Hiwase, TP Hughes and DL White
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.
Keywords: Humans; Blast Crisis; Transforming Growth Factor alpha; Interleukin-6; Cytokines; Prognosis; Disease-Free Survival; Remission Induction; Lymphocyte Activation; Time Factors; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Precision Medicine
RMID: 0030043887
DOI: 10.1038/leu.2016.34
Appears in Collections:Medicine publications

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