Plasma Elastase Screening in Hematological Disease Reveals Its Potential as a Diagnostic and Prognostic Biomarker in Hematological Malignancies

Introduction: Neutrophil-extracellular traps are net-like material released by triggered neutrophils and composed of decondensed chromatin linked to nuclear proteins. Elastase, one of the fourth most represented neutrophil-specific serine proteases stored in azurophil granules of naïve neutrophils, exerts various actions, including degradation of extracellular matrix and has proinflammatory functions. Methods: Plasma was obtained from 111 patients with various hematological malignancies and 42 healthy donors, and plasma elastase levels were measured by ELISA. Results: Reduced circulating levels of neutrophil elastase were found in patients with myelodysplastic syndromes (MDS) and chronic lymphocytic leukemia, while they were increased in acute myeloid leukemia (AML) and non-Hodgkin lymphomas (NHL), with statistically significant AUCs (AML, AUC = 0.7821 and p = 0.0182; and NHL, AUC = 0.7521 and p = 0.0008). Moreover, multiple patients with standard-risk genetic features tended to have higher plasma elastase levels compared to healthy controls. Patients were then divided into two groups, using a cut-off of 300 ng/mL of plasma elastase, and clinical outcomes were compared, showing reduced overall survival and progression-free survival in those subjects with increased plasma elastase levels, as well as shorter time-to-treatment. Conclusion: Our findings indicate that circulating plasma elastase could be useful to distinguish across diseases in the differential diagnosis of hematological malignancies, and could be used as additional prognostic biomarker of disease progression and responsiveness to therapies.