RHOF activation of AKT/β-catenin signaling pathway drives acute myeloid leukemia progression and chemotherapy resistance
Xin Wen,
Peng Li,
Yuechan Ma,
Dongmei Wang,
Ruinan Jia,
Yuan Xia,
Wei Li,
Yongjian Li,
Guosheng Li,
Tao Sun,
Fei Lu,
Jingjing Ye,
Chunyan Ji
Affiliations
Xin Wen
Department of Hematology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250012, People’s Republic of China
Peng Li
Department of Hematology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250012, People’s Republic of China
Yuechan Ma
Department of Hematology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250012, People’s Republic of China
Dongmei Wang
Shandong Key Laboratory of Immunohematology, Qilu Hospital, Shandong University, Jinan 250012, People’s Republic of China
Ruinan Jia
Department of Hematology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250012, People’s Republic of China
Yuan Xia
Department of Hematology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250012, People’s Republic of China
Wei Li
Department of Hematology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250012, People’s Republic of China
Yongjian Li
Department of Hematology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250012, People’s Republic of China
Guosheng Li
Department of Hematology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250012, People’s Republic of China; Shandong Key Laboratory of Immunohematology, Qilu Hospital, Shandong University, Jinan 250012, People’s Republic of China
Tao Sun
Department of Hematology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250012, People’s Republic of China; Shandong Key Laboratory of Immunohematology, Qilu Hospital, Shandong University, Jinan 250012, People’s Republic of China
Fei Lu
Department of Hematology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250012, People’s Republic of China; Corresponding author
Jingjing Ye
Department of Hematology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250012, People’s Republic of China; Shandong Key Laboratory of Immunohematology, Qilu Hospital, Shandong University, Jinan 250012, People’s Republic of China
Chunyan Ji
Department of Hematology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250012, People’s Republic of China; Shandong Key Laboratory of Immunohematology, Qilu Hospital, Shandong University, Jinan 250012, People’s Republic of China; Corresponding author
Summary: Acute myeloid leukemia (AML) is a clonal malignancy originating from leukemia stem cells, characterized by a poor prognosis, underscoring the necessity for novel therapeutic targets and treatment methodologies. This study focuses on Ras homolog family member F, filopodia associated (RHOF), a Rho guanosine triphosphatase (GTPase) family member. We found that RHOF is overexpressed in AML, correlating with an adverse prognosis. Our gain- and loss-of-function experiments revealed that RHOF overexpression enhances proliferation and impedes apoptosis in AML cells in vitro. Conversely, genetic suppression of RHOF markedly reduced the leukemia burden in a human AML xenograft mouse model. Furthermore, we investigated the synergistic effect of RHOF downregulation and chemotherapy, demonstrating significant therapeutic efficacy in vivo. Mechanistically, RHOF activates the AKT/β-catenin signaling pathway, thereby accelerating the progression of AML. Our findings elucidate the pivotal role of RHOF in AML pathogenesis and propose RHOF inhibition as a promising therapeutic approach for AML management.
