Neutrophils in chronic lymphocytic leukemia are permanently activated and have functional defects

Gayane Manukyan; Tomas Papajik; Petr Gajdos; Zuzana Mikulkova; Renata Urbanova; Gabriela Gabcova; Milos Kudelka; Peter Turcsányi; Pavlina Ryznerova; Vit Prochazka; Eva Kriegova

doi:10.18632/oncotarget.20031

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Research Papers:

Neutrophils in chronic lymphocytic leukemia are permanently activated and have functional defects

Gayane Manukyan, Tomas Papajik, Petr Gajdos, Zuzana Mikulkova, Renata Urbanova, Gabriela Gabcova, Milos Kudelka, Peter Turcsányi, Pavlina Ryznerova, Vit Prochazka and Eva Kriegova _

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Oncotarget. 2017; 8:84889-84901. https://doi.org/10.18632/oncotarget.20031

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Abstract

Gayane Manukyan1,4, Tomas Papajik2, Petr Gajdos3, Zuzana Mikulkova1, Renata Urbanova2, Gabriela Gabcova1, Milos Kudelka3, Peter Turcsányi2, Pavlina Ryznerova2, Vit Prochazka2 and Eva Kriegova1

1 Department of Immunology, Faculty of Medicine and Dentistry, Palacky University Olomouc, Olomouc, Czech Republic

2 Department of Hemato-Oncology, Faculty of Medicine and Dentistry, Palacky University and University Hospital, Olomouc, Czech Republic

3 Department of Computer Science, Faculty of Electrical Engineering and Computer Science, VSB-Technical University of Ostrava, Ostrava, Czech Republic

4 Laboratory of Molecular and Cellular Immunology, Institute of Molecular Biology NAS RA, Yerevan, Armenia

Correspondence to:

Eva Kriegova, email: [email protected]

Keywords: chronic lymphocytic leukemia, neutrophils, disease activity, flow cytometry, enhanced ROS production

Received: May 23, 2017 Accepted: July 25, 2017 Published: August 08, 2017

Abstract

A growing body of studies highlights involvement of neutrophils in cancer development and progression. Our aim was to assess the phenotypic and functional properties of circulating neutrophils from patients with chronic lymphocytic leukemia (CLL). The percentage of CD54+ and CD64+ neutrophils as well as CD54 expression on these cells were higher in CLL patients than in age-matched healthy controls. Neutrophils from CLL produced more reactive oxygen species (ROS) compared to controls in both resting and activated conditions. Lipopolysaccharide-induced production of IL-1β and TNF-a as well as reduced TLR2 expression in neutrophils from CLL than in neutrophils from controls suggesting their tolerant state. Finally, phenotypic alterations of neutrophils, particularly elevation of CD64 and CD54 markers, correlated with disease activity and treatment, and low percentage of neutrophils. Taken together, the alterations in percentage and functional characteristics of neutrophils reflect the clinical course of CLL. Our data provide first evidence that neutrophils in CLL are permanently primed and have functional defects.

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Research Papers:

Neutrophils in chronic lymphocytic leukemia are permanently activated and have functional defects

Abstract