title: Expression of surface-associated 82kDa-proMMP-9 in primary acute leukemia blast cells inversely correlates with patients' risk.
abstract: With its ability to degrade extracellular matrix proteins and activate growth factors and cytokines, matrix metalloproteinase (MMP)-9 is an important regulator of cell function. Previously, we reported that myeloid leukemic cells express a unique 82kDa-proMMP-9 variant on their cell surface that is not affected by its natural inhibitor. In this study, we generated monoclonal antibodies that specifically recognize 82kDa-proMMP-9. Flow cytometry analysis using these antibodies revealed significant surface expression of 82kDa-proMMP-9 in monocytes, but minimal amounts in T and B cells isolated from peripheral blood of nine healthy donors and 22 patients with acute myeloid leukemia (AML). In all AML patients, blasts expressed 82kDa-proMMP-9 at levels of 4%-46%, with significantly higher levels in patients with a better risk defined according to National Comprehensive Cancer Network (NCCN) guidelines (ρ = -0.748, p < 0.001) and favorable phenotype according to the French-American-British classification (p = 0.02) compared with patients with adverse prognoses. Receiver operating characteristic curve analysis confirmed the diagnostic accuracy of 82kDa-proMMP-9 measurement in AML blasts (area under the curve: 0.893 [0.739-1.000], p = 0.019). It led us to define a cutoff value of 11.5% for identifying patients with lower NCCN risk (p = 0.005) and with a tendency toward a higher probability of response to anthracycline-based therapy (p = 0.109) and increased event-free survival (p = 0.24). Thus, 82kDa-proMMP-9 expression on blasts may represent a novel independent marker of prognosis in patients with AML.
authors: University of Minnesota Masonic Cancer Center, Section of Molecular Cancer Therapeutics, Therapeutic Radiology-Radiation Oncology, University of Minnesota, Minneapolis, MN; Department for Hematology and Oncology, Eberhard Karls University, Tuebingen, Germany.
authors: Joerg
authors: J
authors: Schmohl
authors: Institute for Cardiovascular Prevention, Ludwig Maximilians University of Munich, Munich, Germany; European Center of Excellence on Atherosclerosis, Hypertension and Dyslipidemia, G. d'Annunzio University, Chieti, Italy.
authors: Donato
authors: D
authors: Santovito
authors: Department for Hematopoietic Cell Transplantation, Department of Medicine 3, University Hospital of Munich, Munich, Germany.
authors: Thomas
authors: T
authors: Guenther
authors: Department for Hematopoietic Cell Transplantation, Department of Medicine 3, University Hospital of Munich, Munich, Germany.
authors: Wishnu
authors: W
authors: Sutanto
authors: Department for Hematopoietic Cell Transplantation, Department of Medicine 3, University Hospital of Munich, Munich, Germany.
authors: Tanja
authors: T
authors: Kroell
authors: Department for Hematology and Oncology, Eberhard Karls University, Tuebingen, Germany.
authors: Helmut
authors: H
authors: Salih
authors: Institute for Cardiovascular Prevention, Ludwig Maximilians University of Munich, Munich, Germany.
authors: Thomas
authors: T
authors: Pitsch
authors: Institute for Cardiovascular Prevention, Ludwig Maximilians University of Munich, Munich, Germany.
authors: Virginia
authors: V
authors: Egea
authors: Institute for Cardiovascular Prevention, Ludwig Maximilians University of Munich, Munich, Germany.
authors: Christian
authors: C
authors: Weber
authors: Department for Hematopoietic Cell Transplantation, Department of Medicine 3, University Hospital of Munich, Munich, Germany.
authors: Helga
authors: H
authors: Schmetzer
authors: Institute for Cardiovascular Prevention, Ludwig Maximilians University of Munich, Munich, Germany. Electronic address: christian.ries@med.uni-muenchen.de.
authors: Christian
authors: C
authors: Ries
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018943:Anthracyclines / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000378:metabolism; D001854:Bone Marrow Cells / Q000378:metabolism*; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D004792:Enzyme Precursors / Q000737:chemistry / Q000378:metabolism*; D005260:Female; D006801:Humans; D060828:Induction Chemotherapy / Q000379:methods; D053208:Kaplan-Meier Estimate; D007951:Leukemia, Myeloid / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000737:chemistry / Q000378:metabolism*; D008875:Middle Aged; D008970:Molecular Weight; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D011379:Prognosis; D012307:Risk Factors; D020298:U937 Cells; D055815:Young Adult
chemical_list: D018943:Anthracyclines; D014408:Biomarkers, Tumor; D004792:Enzyme Precursors; C120487:pro-matrix metalloproteinase 9; D020780:Matrix Metalloproteinase 9