Regulation of coagulation activation in newly diagnosed AML by the heme enzyme myeloperoxidase.

Autor: Langer F; Oncology, Hematology and BMT with section of Pneumology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Quick H; Oncology, Hematology and BMT with section of Pneumology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Beitzen-Heineke A; Oncology, Hematology and BMT with section of Pneumology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Janjetovic S; Klinik für Hämatologie und Zelltherapie, Helios Klinikum Berlin-Buch, Berlin, Germany., Mäder J; Oncology, Hematology and BMT with section of Pneumology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Lehr C; Oncology, Hematology and BMT with section of Pneumology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Bokemeyer C; Oncology, Hematology and BMT with section of Pneumology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Kuta P; Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Renné T; Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Irish Centre for Vascular Biology, School of Pharmacy and Biomolecular Sciences, Royal College of Surgeons in Ireland, Dublin, Ireland; Center for Thrombosis and Hemostasis (CTH), Johannes Gutenberg University Medical Center, Mainz, Germany., Fiedler W; Oncology, Hematology and BMT with section of Pneumology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Beckmann L; Oncology, Hematology and BMT with section of Pneumology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Klingler F; Oncology, Hematology and BMT with section of Pneumology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Rolling CC; Oncology, Hematology and BMT with section of Pneumology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. Electronic address: c.rolling@uke.de.
Jazyk: angličtina
Zdroj: Thrombosis research [Thromb Res] 2023 Sep; Vol. 229, pp. 155-163. Date of Electronic Publication: 2023 Jul 12.
DOI: 10.1016/j.thromres.2023.07.006
Abstrakt: Introduction: Patients with acute myeloid leukemia (AML) are at increased risk of thrombohemorrhagic complications. Overexpressed tissue factor (TF) on AML blasts contributes to systemic coagulation activation. We have recently shown that the heme enzyme myeloperoxidase (MPO) negatively regulates TF procoagulant activity (PCA) on myelomonocytic cells in vitro. We now aimed to further characterize the functional interaction of MPO and TF in AML in vivo.
Methods: We prospectively recruited 66 patients with newly diagnosed AML. TF PCA of isolated peripheral blood mononuclear cells (PBMC) was assessed by single-stage clotting assay in the presence or absence of inhibitors against MPO catalytic activity (ABAH) or against MPO-binding integrins (anti-CD18). MPO in plasma and in AML blasts was measured by ELISA, and plasma D-dimers and prothrombin fragment F1+2 were quantified by automated immunoturbidimetric and chemiluminescence assays, respectively.
Results: Patients with AML had significantly higher MPO plasma levels compared to healthy controls and exhibited increased levels of D-dimers and F1+2. In vivo thrombin generation was mediated by TF PCA on circulating PBMC. Ex vivo incubation of isolated PBMC with ABAH or anti-CD18 antibody resulted in either increased or decreased TF PCA. The strong and robust correlation of F1+2 with TF PCA of circulating PBMC was abrogated at MPO plasma levels higher than 150 ng/mL, indicating a modulatory role for MPO on TF-mediated in vivo thrombin generation above this threshold.
Conclusion: Our study indicates that catalytically active MPO released by circulating myeloblasts regulates TF-dependent coagulation in patients with newly diagnosed AML in a CD18-dependent manner.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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