Mei_2021_Oncol.Rep_45_641

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 alpha (FAPalpha) 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 FAPalpha in BM with clinical parameters and survival of newly diagnosed patients with AML. Subsequently, the protective effect of FAPalpha 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 FAPalpha 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 FAPalpha using siRNA decreased this protection. It was found that Kasumi-1 cells expressed beta-catenin, which could be inhibited by Ara-C, and beta-catenin expression was significantly activated when co-cultured with BMMSCs, even in the presence of Ara-C. Knockdown of FAPalpha with siRNA significantly suppressed the expression of beta-catenin. The present results indicated that FAPalpha serves an important role in the AML BM microenvironment, and that increased expression of FAPalpha 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 FAPalpha, and may occur via the beta-catenin signaling pathway.