title: Expression of 4-1BB and its ligand on blasts correlates with prognosis of patients with AML.
abstract: Costimulatory ligands (COLs) and their receptors (COR) regulate immune reactions and cellular survival and might be relevant in acute myeloid leukemia (AML). This study evaluated the clinical relevance of 4-1BBL, glucocorticoid-induced TNFR-related protein (GITR) and ligand (GITRL), CD80, and CD86 in case of expression on AML blasts. 98 patients were evaluated at initial diagnosis. Immunophenotypically evaluated specific fluorescence index (SFI) levels of COR and COL on blasts were correlated with morphological, cytogenetic, and several prognostic parameters. Significantly higher COR expression was seen in monocytic versus non-monocytic AML subtypes; GITR, p=0.05; GITRL, p=0.005; CD86, p=0.001). Cut-off values for two COR and their ligands were evaluated: cases presenting with 4-1BB values above cut-off 1.2 SFI levels correlated (tendentially) significantly with a higher probability for disease-free survival (DFS, p=0.06) and a favorable HR of 0.2; p=0.04 for relapse. HR for death was also significantly lower in this group (0.12; p=0.04). In contrast, a lower probability for DFS and overall survival was seen in cases with 4-1BBL expression above 2.2 SFI levels (p=0.08 and p=0.09). In addition, multivariate analysis showed a significantly higher probability of death in this group (HR 10.3, p=0.04). Expression of CD80 and CD86 did not show significant prognostic relevance. On initial diagnosis, 4-1BB and 4-1BBL qualify as markers for prediction of patients' course and represent a valuable screening target for patients with AML at initial diagnosis.
authors.affiliation: Section of Molecular Cancer Therapeutics, Therapeutic Radiology-Radiation Oncology, University of Minnesota, Masonic Cancer Center, Minneapolis, Minnesota, USA.|Department of Hematology and Oncology, Medical Department 2, University Hospital of Tuebingen, Tuebingen, Germany.
authors.forename: Joerg U
authors.initials: JU
authors.lastname: Schmohl
authors.affiliation: Department of Hematology and Oncology, Medical Department 2, University Hospital of Tuebingen, Tuebingen, Germany.|Clinical Collaboration Unit Translational Immunology, Department for Internal Medicine II, German Cancer Consortium and German Cancer Research Center, Partner site Tuebingen, Eberhard Karls University Tuebingen, Tuebingen, Germany.
authors.forename: Tina
authors.initials: T
authors.lastname: Nuebling
authors.affiliation: Department of Hematology and Oncology, Medical Department 2, University Hospital of Tuebingen, Tuebingen, Germany.|Clinical Collaboration Unit Translational Immunology, Department for Internal Medicine II, German Cancer Consortium and German Cancer Research Center, Partner site Tuebingen, Eberhard Karls University Tuebingen, Tuebingen, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Wild
authors.affiliation: Department for Hematopoetic Cell Transplantation, Medical Department 3, University Hospital of Munich, Munich, Germany.
authors.forename: Tanja
authors.initials: T
authors.lastname: Kroell
authors.affiliation: Department of Hematology and Oncology, Medical Department 2, University Hospital of Tuebingen, Tuebingen, Germany.
authors.forename: Lothar
authors.initials: L
authors.lastname: Kanz
authors.affiliation: Department of Hematology and Oncology, Medical Department 2, University Hospital of Tuebingen, Tuebingen, Germany.|Clinical Collaboration Unit Translational Immunology, Department for Internal Medicine II, German Cancer Consortium and German Cancer Research Center, Partner site Tuebingen, Eberhard Karls University Tuebingen, Tuebingen, Germany.
authors.forename: Helmut R
authors.initials: HR
authors.lastname: Salih
authors.affiliation: Department for Hematopoetic Cell Transplantation, Medical Department 3, University Hospital of Munich, Munich, Germany.
authors.forename: Helga
authors.initials: H
authors.lastname: Schmetzer
mesh_terms: D053330:4-1BB Ligand / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001752:Blast Crisis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D020869:Gene Expression Profiling; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000473:pathology; D015999:Multivariate Analysis; D009363:Neoplasm Proteins / Q000378:metabolism; D011379:Prognosis; D012307:Risk Factors; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9 / Q000378:metabolism*; D055815:Young Adult
chemical_list: D053330:4-1BB Ligand; D009363:Neoplasm Proteins; C505714:TNFRSF9 protein, human; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9
keywords: Leukemia, Myeloid, Acute; Prognosis