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Myelodysplastic syndrome

Heterogeneous expression of cytokines accounts for clinical diversity and refines prognostication in CMML

Abstract

Chronic myelomonocytic leukemia (CMML) is a clinically heterogeneous neoplasm in which JAK2 inhibition has demonstrated reductions in inflammatory cytokines and promising clinical activity. We hypothesize that annotation of inflammatory cytokines may uncover mutation-independent cytokine subsets associated with novel CMML prognostic features. A Luminex cytokine profiling assay was utilized to profile cryopreserved peripheral blood plasma from 215 CMML cases from three academic centers, along with center-specific, age-matched plasma controls. Significant differences were observed between CMML patients and healthy controls in 23 out of 45 cytokines including increased cytokine levels in IL-8, IP-10, IL-1RA, TNF-α, IL-6, MCP-1/CCL2, hepatocyte growth factor (HGF), M-CSF, VEGF, IL-4, and IL-2RA. Cytokine associations were identified with clinical and genetic features, and Euclidian cluster analysis identified three distinct cluster groups associated with important clinical and genetic features in CMML. CMML patients with decreased IL-10 expression had a poor overall survival when compared to CMML patients with elevated expression of IL-10 (P = 0.017), even when adjusted for ASXL1 mutation and other prognostic features. Incorporating IL-10 with the Mayo Molecular Model statistically improved the prognostic ability of the model. These established cytokines, such as IL-10, as prognostically relevant and represent the first comprehensive study exploring the clinical implications of the CMML inflammatory state.

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Acknowledgements

This research was supported in part by the USF GME Research Grant. Research was funded by EP.

Author contributions

Conception and design: EP and ES; administrative support: EP; provision of study materials or patients: ES, EP, VS, and MWD; collection and assembly of data: ADP, SN, NL, J-MZ, BF, SS, MB, MB, JR, CC, and EP; data analysis and interpretation: MWD, EP, BLF, J-MZ, SN, NL, MB, and JR.

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Correspondence to Eric Padron.

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Niyongere, S., Lucas, N., Zhou, JM. et al. Heterogeneous expression of cytokines accounts for clinical diversity and refines prognostication in CMML. Leukemia 33, 205–216 (2019). https://doi.org/10.1038/s41375-018-0203-0

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