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Longitudinal Cytokine Profiling Identifies GRO-alpha and EGF as Potential Biomarkers of Disease Progression in Essential Thrombocythemia

Obro NF, Grinfeld J, Belmonte M, Irvine M, Shepherd MS, Rao TN, Karow A, Riedel LM, Harris OB, Baxter EJ, Nangalia J, Godfrey A, Harrison CN, Li J, Skoda RC, Campbell PJ, Green AR, Kent DG (2020)

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Publication Type: Journal article

Publication year: 2020

Journal

Book Volume: 4

Journal Issue: 3

DOI: 10.1097/HS9.0000000000000371

Abstract

Myeloproliferative neoplasms (MPNs) are characterized by deregulation of mature blood cell production and increased risk of myelofibrosis (MF) and leukemic transformation. Numerous driver mutations have been identified but substantial disease heterogeneity remains unexplained, implying the involvement of additional as yet unidentified factors. The inflammatory microenvironment has recently attracted attention as a crucial factor in MPN biology, in particular whether inflammatory cytokines and chemokines contribute to disease establishment or progression. Here we present a large-scale study of serum cytokine profiles in more than 400 MPN patients and identify an essential thrombocythemia (ET)-specific inflammatory cytokine signature consisting of Eotaxin, GRO-alpha and EGF. Levels of 2 of these markers (GRO-alpha and EGF) in ET patients were associated with disease transformation in initial sample collection (GRO-alpha) or longitudinal sampling (EGF). In ET patients with extensive genomic profiling data (n=183) cytokine levels added significant prognostic value for predicting transformation from ET to MF. Furthermore, CD56(+)CD14(+) proinflammatory monocytes were identified as a novel source of increased GRO-alpha levels. These data implicate the immune cell microenvironment as a significant player in ET disease evolution and illustrate the utility of cytokines as potential biomarkers for reaching beyond genomic classification for disease stratification and monitoring.

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How to cite

APA:

Obro, N.F., Grinfeld, J., Belmonte, M., Irvine, M., Shepherd, M.S., Rao, T.N.,... Kent, D.G. (2020). Longitudinal Cytokine Profiling Identifies GRO-alpha and EGF as Potential Biomarkers of Disease Progression in Essential Thrombocythemia. HemaSphere, 4(3). https://dx.doi.org/10.1097/HS9.0000000000000371

MLA:

Obro, Nina F., et al. "Longitudinal Cytokine Profiling Identifies GRO-alpha and EGF as Potential Biomarkers of Disease Progression in Essential Thrombocythemia." HemaSphere 4.3 (2020).

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