The clinical and prognostic significance of FOXN3 downregulation in acute myeloid leukaemia

Abstract

Acute myeloid leukaemia (AML), the most common type of adult leukaemia, is characterized by out-of-control proliferation, the inhibition of differentiation, the apoptotic blockage of leucocytes and reduction in normal haematopoietic cells. 1,2 With the development of cytogenetic and molecular biology, AML could be diagnosed and treated at the genomic level with a better therapeutic effect. However, 60%-80% of AML patients could not be cured due to disease resistance and recurrence. [3][4][5][6][7][8] Recent studies that focused on abnormal transcription demonstrate the key role of transcription regulators in leukaemogenesis and suggest a potential therapeutic strategy for AML. 5 Therefore, the identification of novel abnormal transcription factors and their functions in AML will provide new clues on the pathogenesis and treatment of AML. The transcription factor forkhead box N3 (FOXN3), as a member of the forkhead box N superfamily, participates in several biological processes, including the cell cycle, cell differentiation, epithelial-mesenchymal transition, gene transcription and glucose metabolism. 9-13 Previous studies have shown that the downregulated expression of FOXN3 is observed in various malignancies, such as hepatocellular carcinoma (HCC), colon cancer, ERα-positive breast cancer, Hodgkin lymphoma, head and neck cancer, lung cancer, adult glioblastoma multiforme, T cell acute lymphoblastic leukaemia (ALL)and osteosarcoma, 9,10,12,[14][15][16][17][18][19] and the FOXN3 expression level is associated with the prognosis of some cancers. Abstract Introduction: The expression of forkhead box N3 (FOXN3), also known as checkpoint suppressor 1 (CHES1), is reduced in many types of tumours. However, the clinical significance of FOXN3 and its potential role in acute myeloid leukaemia (AML) remain largely unknown. Methods: A total of 117 de novo AML patients newly diagnosed between December 2015 and January 2018 were included in this study. The expression of FOXN3 and its clinical significance were analysed in these AML patients. Results: The expression of FOXN3 was significantly downregulated in AML. In addition, lower FOXN3 expression was associated with older age and higher white blood cell counts. Moreover, a close correlation was observed between lower FOXN3 expression and a lower complete remission (CR) rate and shorter overall survival (OS), which was further analysed by multivariate analysis. Conclusion: These data suggest that FOXN3 is a novel biomarker in AML and that lower FOXN3 expression predicts poor chemotherapy response and prognosis in AML. K E Y W O R D S acute myeloid leukaemia, chemotherapy response, diagnosis, FOXN3, prognosis | 271 ZHANG et Al.Although lower FOXN3 expression in adult AML was found in our previous study, 20,21 its clinical and prognostic significance in AML remains unknown. Our study investigated the expression profile of FOXN3 in the bone marrow (BM) of adult AML patients and analysed its clinical significance.

An Integrated Study on the Differential Expression of the FOX Gene Family in Cancer and Their Response to Chemotherapy Drugs

“…Consistent with our finding, several lines of evidence have recently highlighted the roles of FOXN3 [ 42 ], FOXO3 [ 43 ], FOXO4 [ 16 ], and FOXP3 [ 44 ] in leukemia. In this light, based on the fully elucidation of pathogenic mechanisms of these genes, the identification of new medicine targeting these genes could be considered as a novel clue provided for effective systemic therapy.…”

Tumor suppressors in acute myeloid leukemia

“…In addition, Forkhead box protein N3 (FOXN3) plays a key role in cell cycle regulation and FOXN3 expression levels have been shown to negatively correlate with leukocyte numbers in AML patients. In line, FOXN3 levels are frequently decreased in AML patients and cell lines [32,60].…”

MAGI2-AS3 Modulates Proliferation, Apoptosis and Glycolysis in Acute Lymphoblastic Leukemia via miR-452-5p/FOXN3 Axis

“…Forkhead box N3 (FOXN3), a member of forkhead box family, is involved various pathophysiological processes, including tumorigenesis [17]. As reported by previous researches, a decreased expression of FOXN3 is con rmed in a wide variety of tumors, including ALL [18,19].…”