Expression and role of fibroblast activation protein α in acute myeloid leukemia

Currently, the prognosis of acute myeloid leukemia (AML) is poor. In the AML microenvironment, bone marrow (BM) mesenchymal stem cells (BMMSCs) serve an important role in protecting AML cells from chemotherapy-induced apoptosis. The present study aimed to evaluate the expression of fibroblast activation protein α (FAPα) in BMMSCs and BM biopsy samples via flow cytometry, reverse transcription-quantitative PCR and immunohistochemistry, as well as to identify the correlation between the expression of FAPα in BM with clinical parameters and survival of newly diagnosed patients with AML. Subsequently, the protective effect of FAPα on Cytosine arabinoside (Ara-C)-induced apoptosis in Kasumi-1 cells was investigated via small interfering (si)RNA, and its underlying mechanism was examined by western blotting. The results demonstrated significant differences in FAPα expression in BMMSCs and BM biopsy samples between patients with AML and healthy donors. Furthermore, BMMSCs protected Ara-C-induced Kasumi-1 cells from apoptosis, and knockdown of FAPα using siRNA decreased this protection. It was found that Kasumi-1 cells expressed β-catenin, which could be inhibited by Ara-C, and β-catenin expression was significantly activated when co-cultured with BMMSCs, even in the presence of Ara-C. Knockdown of FAPα with siRNA significantly suppressed the expression of β-catenin. The present results indicated that FAPα serves an important role in the AML BM microenvironment, and that increased expression of FAPα in BM may be a poor prognostic factor in patients with AML. Moreover, the current findings demonstrated that BMMSCs protected AML cells from apoptosis, which was in part contributed by FAPα, and may occur via the β-catenin signaling pathway.