PB1042 - Coagulation activation in newly diagnosed AML is regulated by the heme enzyme myeloperoxidase.

Tuesday, July 12, 2022

6:30 PM – 7:30 PM

Location: Exhibition

Presentation Format: In-Person

Co-Author(s)

CR

Christina C. Rolling

Specialist physician
II. Medizinische Klinik und Poliklinik, Zentrum für Onkologie, UKE, Hamburg, Germany
Hamburg, Hamburg, Germany

Presenting Author(s)

Hanna Quick

MD student
UKE, Hamburg, Germany
Hamburg, Hamburg, Germany

Co-Author(s)

AB

Antonia Beitzen-Heineke

Physician
II. Medizinische Klinik und Poliklinik, Zentrum für Onkologie, UKE, Hamburg, Germany
Hamburg, Hamburg, Germany
SJ

Snjezana Janjetovic

Attending physician
Helios Klinikum Berlin-Buch, Berlin, Germany
Berlin, Berlin, Germany
JM

Jonathan Mäder

MD student
II. Medizinische Klinik und Poliklinik, Zentrum für Onkologie, UKE, Hamburg, Germany
Hamburg, Hamburg, Germany
CL

Carina Lehr

Research technician
II. Medizinische Klinik und Poliklinik, Zentrum für Onkologie, UKE, Hamburg, Germany
Hamburg, Hamburg, Germany
CB

Carsten Bokemeyer

Head of Department
II. Medizinische Klinik und Poliklinik, Zentrum für Onkologie, UKE, Hamburg, Germany
Hamburg, Hamburg, Germany
MH

Munif Haddad

Attending physician
Institut für Klinische Chemie und Laboratoriumsmedizin, Zentrum für Diagnostik, UKE, Hamburg, Germany
Hamburg, Hamburg, Germany
TR

Thomas Renné

Head of Department
Institut für Klinische Chemie und Laboratoriumsmedizin, Zentrum für Diagnostik, UKE, Hamburg, Germany
Hamburg, Hamburg, Germany
WF

Walter Fiedler

Attending physician
II. Medizinische Klinik und Poliklinik, Zentrum für Onkologie, UKE, Hamburg, Germany
Hamburg, Hamburg, Germany
Lennart Beckmann

Physician
Zentrum für Onkologie, UKE, Hamburg, Germany
Hamburg, Hamburg, Germany
FK

Felix Klingler

Physician
II. Medizinische Klinik und Poliklinik, Zentrum für Onkologie, UKE, Hamburg, Germany
Hamburg, Hamburg, Germany
FL

Florian Langer

Medical Specialist in Internal Medicine
Universitätsklinikum Eppendorf, II. Medizinische Klinik und Poliklinik, Hubertus Wald Tumorzentrum, Universitäres Cancer Center Hamburg (UCCH), Hamburg, Germany
Hamburg, Hamburg, Germany

Background: Patients with acute myeloid leukemia (AML) are at increased risk of thrombohemorrhagic complications. Overexpressed tissue factor (TF) on circulating AML blasts and shedding of TF-bearing microvesicles (MV) contribute 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.

Aims: Subgroups of AML are characterized by MPO-positive blasts. We therefore wanted to investigate the functional interaction of MPO and TF in AML in vivo.

Methods: We prospectively recruited 67 patients with newly diagnosed AML. The study was approved by the local ethics committee (PV5365). All patients and healthy controls (HC) provided written informed consent. TF PCA of isolated AML blasts was assessed by single-stage clotting assay in the presence or absence of inhibitors against MPO catalytic activity (ABAH) or against surface MPO-binding integrins (anti-CD18). MV-associated TF PCA was measured by chromogenic Xa generation assay. Plasma and intracellular MPO, prothrombin fragment F1+2 were analyzed by commercial ELISAs and D-dimers by an immunoturbidimetric assay.

Results: AML patients had significantly higher MPO plasma levels compared to HC. Plasma MPO correlated with MPO-positive circulating leukemic blasts and with intracellular MPO. Ex vivo incubation of isolated AML blasts with ABAH or anti-CD18 either increased or decreased TF PCA, suggesting a divergent regulatory effect of MPO on TF activity. Importantly, modulation of TF by MPO catalytic activity required integrin-dependent surface binding of the heme enzyme.
Cellular TF PCA and F1+2 plasma levels strongly correlated, indicating that circulating leukemic blasts contributed to systemic coagulation activation in AML. In support of a regulatory role for MPO on TF, this effect was mitigated in patients with MPO plasma levels above the median.

Conclusion(s): Our study suggests that catalytically active MPO released by circulating myeloblasts regulates TF-dependent coagulation activation in patients with newly diagnosed AML in a CD18-dependent manner.