PT  - JOURNAL ARTICLE
AU  - Joerg U Schmohl
AU  - Tina Nuebling
AU  - Julia Wild
AU  - Tanja Kroell
AU  - Lothar Kanz
AU  - Helmut R Salih
AU  - Helga Schmetzer
TI  - Expression of 4-1BB and its ligand on blasts correlates with prognosis of patients with AML
AID  - 10.1136/jim-2016-000081
DP  - 2016 Dec 01
TA  - Journal of Investigative Medicine
PG  - 1252--1260
VI  - 64
IP  - 8
4099  - http://hw-f5-jim.highwire.org/content/64/8/1252.short
4100  - http://hw-f5-jim.highwire.org/content/64/8/1252.full
SO  - J Investig Med2016 Dec 01; 64
AB  - 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.