title: Disease dynamics in patients with acute myeloid leukemia: new biomarkers.
abstract: Acute myeloid leukemia (AML) is characterized by rapid growth of leukemic blast cells. Extracellular vesicles (EVs), shedding from various cells, express antigens, reflecting their cellular origin. The current study was designed to explore the role of circulating EVs as potential biomarkers of AML activity and predictors of thrombogenicity in patients with this malignancy. Blood samples were collected from healthy controls and patients with newly diagnosed AML at three time points: diagnosis, nadir, and remission. EV concentration, cell origin, and expression of coagulation proteins were characterized using fluorescence-activated cell sorting. EV cytokine contents were evaluated by protein array. Procoagulant activity was assessed using Factor Xa chromogenic assay. Forty-two AML patients were enrolled in the study. Total EV numbers were higher in patients in first remission compared with controls, whereas blast EV counts were higher in patients at diagnosis compared with controls and patients in remission. Blast EV levels were significantly lower in patients who achieved remission and were alive at 3-year follow up compared with their succumbed counterparts. At all three time points, percentage of endothelial EVs was higher in patients compared with controls. EV procoagulant activity was elevated at diagnosis and in remission, and, unlike controls' EVs, patients' EVs increased endothelial cell thrombogenicity. EVs of AML patients express membrane proteins of blast cells and might serve as biomarkers of leukemia dynamics and presence of minimal residual disease. Increased levels of endothelial EVs and their procoagulant activity may indicate a vascular injury associated with a hypercoagulable state in AML.
authors.affiliation: Department of Hematology and Bone Marrow Transplantation, Rambam Health Care Campus, Haifa, Israel; Internal Medicine C, Rambam Health Care Campus, Haifa, Israel; Bruce Rappaport Faculty of Medicine, Technion, Israel Institute of Technology, Haifa, Israel. Electronic address: i_tzoran@rambam.health.gov.il.
authors.forename: Inna
authors.initials: I
authors.lastname: Tzoran
authors.affiliation: Department of Hematology and Bone Marrow Transplantation, Rambam Health Care Campus, Haifa, Israel; Bruce Rappaport Faculty of Medicine, Technion, Israel Institute of Technology, Haifa, Israel.
authors.forename: Annie
authors.initials: A
authors.lastname: Rebibo-Sabbah
authors.affiliation: Department of Hematology and Bone Marrow Transplantation, Rambam Health Care Campus, Haifa, Israel; Bruce Rappaport Faculty of Medicine, Technion, Israel Institute of Technology, Haifa, Israel.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Brenner
authors.affiliation: Department of Hematology and Bone Marrow Transplantation, Rambam Health Care Campus, Haifa, Israel; Bruce Rappaport Faculty of Medicine, Technion, Israel Institute of Technology, Haifa, Israel.
authors.forename: Anat
authors.initials: A
authors.lastname: Aharon
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000097:blood*; D055252:Cell-Derived Microparticles / Q000378:metabolism*; D015951:Factor Xa / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000097:blood*; D008297:Male; D009363:Neoplasm Proteins / Q000097:blood*; D019851:Thrombophilia / Q000097:blood*
chemical_list: D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D015951:Factor Xa