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Expression of 4-1BB and its ligand on blasts correlates with prognosis of patients with AML
  1. Joerg U Schmohl1,2,
  2. Tina Nuebling2,3,
  3. Julia Wild2,3,
  4. Tanja Kroell4,
  5. Lothar Kanz2,
  6. Helmut R Salih2,3,
  7. Helga Schmetzer4
  1. 1Section of Molecular Cancer Therapeutics, Therapeutic Radiology-Radiation Oncology, University of Minnesota, Masonic Cancer Center, Minneapolis, Minnesota, USA
  2. 2Department of Hematology and Oncology, Medical Department 2, University Hospital of Tuebingen, Tuebingen, Germany
  3. 3Clinical 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
  4. 4Department for Hematopoetic Cell Transplantation, Medical Department 3, University Hospital of Munich, Munich, Germany
  1. Correspondence to Dr Joerg U Schmohl, University Hospital of Tuebingen, Otfried-Mueller Strasse 10, 72076 Tuebingen, Germany; joerg.schmohl{at}


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.

  • Leukemia, Myeloid, Acute
  • Prognosis

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  • Contributors JUS and HS contributed in planning and wrote the manuscript. TN and TK collected the data. JW collected the data and contributed on writing the materials and methods section. LK and HRS contributed in planning.

  • Funding Deutsche Krebshilfe e.V. (JUS) (111548).

  • Competing interests None declared.

  • Patient consent Obtained.

  • Ethics approval Local Ethics Committee (13/2007V).

  • Provenance and peer review Not commissioned; externally peer reviewed.

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