FUS1 is a tumor suppressor gene that has been found to be frequently lost in a variety of solid tumors. In this study, we aimed to investigate the expression status of the FUS1 gene in acute myeloid leukemia (AML), as well as its clinical significance. We further explored the correlation between the expression of FUS1 and miR-378 in AML. We detected expression of the FUS1 transcript in bone marrow mononuclear cells from 23 controls and 158 newly diagnosed AML patients by real-time quantitative polymerase chain reaction. Downregulated FUS1 expression was found in 139 out of 158 (87.97%) AML cases; this rate was significantly lower than that in all 23 controls (p = 0.012). Receiver operating characteristic curve analysis revealed that the FUS1 transcript level could discriminate AML patients from controls effectively (area under the ROC curve = 0.663). Kaplan-Meier analysis demonstrated that non-M3-AML patients with a low FUS1 expression had a shorter overall survival (p = 0.049) and leukemia-free survival (p = 0.051) than those with a high FUS1 expression. Furthermore, we studied the correlation between the expression of FUS1 and miR-378 in 53 newly diagnosed AML patients. We found that the correlation coefficient was –0.346, which showed that FUS1 and miR-378 were negatively correlated in AML patients (p = 0.011). These results indicate that the low expression of FUS1 is a common molecular event in AML.

Lane SW, Scadden DT, Gilliland DG: The leukemic stem cell niche: current concepts and therapeutic opportunities. Blood 2009; 114: 1150–1157.
Mrózek K, Marcucci G, Paschka P, Whitman SP, Bloomfield CD: Clinical relevance of mutations and gene-expression changes in adult acute myeloid leukemia with normal cytogenetics: are we ready for a prognostically prioritized molecular classification? Blood 2007; 109: 431–448.
Grimwade D: The clinical significance of cytogenetic abnormalities in acute myeloid leukaemia. Best Pract Res Clin Haematol 2001; 14: 497–529.
Byrd JC, Mrózek K, Dodge RK, Carroll AJ, Edwards CG, Arthur DC, Pettenati MJ, Patil SR, Rao KW, Watson MS, Koduru PR, Moore JO, Stone RM, Mayer RJ, Feldman EJ, Davey FR, Schiffer CA, Larson RA, Bloomfeld CD; Cancer and Leukemia Group B (CALGB 8461): Pretreatment cytogenetic abnormalities are predictive of induction success, cumulative incidence of relapse, and overall survival in adult patients with de novo acute myeloid leukemia: results from Cancer and Leukemia Group B (CALGB 8461). Blood 2002; 100: 4325–4336.
Haferlach T: Molecular genetic pathways as therapeutic targets in acute myeloid leukemia. Hematology Am Soc Hematol Educ Program 2008, pp 400–411.
Look AT: Oncogenic transcription factors in the human acute leukemias. Science 1997; 278: 1059–1064.
Krug U, Ganser A, Koeffler HP: Tumor suppressor genes in normal and malignant hematopoiesis. Oncogene 2002; 21: 3475–3495.
Vardiman JW, Thiele J, Arber DA, Brunning RD, Borowitz MJ, Porwit A, Harris NL, Le Beau MM, Hellström-Lindberg E, Tefferi A, Bloomfeld CD: The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood 2009; 114: 937–951.
Gulley ML, Shea TC, Fedoriw Y: Genetic tests to evaluate prognosis and predict therapeutic response in acute myeloid leukemia. J Mol Diagn 2010; 12: 3–16.
Lerman MI, Minna JD: The 630-kb lung cancer homozygous deletion region on human chromosome 3p21.3: identification and evaluation of the resident candidate tumor suppressor genes – the International Lung Cancer Chromosome 3p21.3 Tumor. Suppressor Gene Consortium. Cancer Res 2000; 60: 6116–6133.
Ivanova A, Ivanov S, Prudkin L, Nonaka D, Zhandong L, Tsao A, Wistuba I, Roth J, Pass H: Mechanisms of FUS1/TUSC2 deficiency in mesothelioma and its tumorigenic transcriptional effects. Mol Cancer 2009; 8: 91.
Bennett JM, Catovsky D, Daniel MT, Flandrin G, Galton DA, Gralnick HR, Sultan C: Proposed revised criteria for the classification of acute myeloid leukemia: a report of the French-American-British Cooperative Group. Ann Intern Med 1985; 103: 620–625.
Sabattini E, Bacci F, Sagramoso C, Pileri SA: WHO classification of tumours of haematopoietic and lymphoid tissues in 2008: an overview. Pathologica 2010; 102: 83–87.
Li Y, Lin J, Yang J, Qian J, Qian W, Yao DM, Deng ZQ, Liu Q, Chen XX, Xie D, An C, Tang CY: Overexpressed let-7a-3 is associated with poor outcome in acute myeloid leukemia. Leuk Res 2013; 37: 1642–1647.
Lin J, Yao DM, Qian J, Chen Q, Qian W, Li Y, Yang J, Wang CZ, Chai HY, Qian Z, Xiao GF, Xu WR: Recurrent DNMT3A R882 mutations in Chinese patients with acute myeloid leukemia and myelodysplastic syndrome. PLoS One 2011; 6:e26906.
Lin J, Yao DM, Qian J, Chen Q, Qian W, Li Y, Yang J, Wang CZ, Chai HY, Qian Z, Xiao GF, Xu WR: IDH1 and IDH2 mutation analysis in Chinese patients with acute myeloid leukemia and myelodysplastic syndrome. Ann Hematol 2012; 91: 519–525.
Yang X, Qian J, Sun A, Lin J, Xiao G, Yin J, Chen S, Wu D: RAS mutation analysis in a large cohort of Chinese patients with acute myeloid leukemia. Clin Biochem 2013; 46: 579–583.
Qian J, Yao DM, Lin J, Qian W, Wang CZ, Chai HY, Yang J, Li Y, Deng ZQ, Ma JC, Chen XX: U2AF1 mutations in Chinese patients with acute myeloid leukemia and myelodysplastic syndrome. PLoS One 2012; 7:e45760.
Bartel DP: MicroRNAs: target recognition and regulatory functions. Cell 2009; 136: 215–233.
Lee DY, Deng Z, Wang C-H, Yang BB: MicroRNA-378 promotes cell survival, tumor growth, and angiogenesis by targeting SuFu and Fus-1 expression. Proc Natl Acad Sci USA 2007; 104: 20350–20355.
Chen LT, Xu SD, Xu H, Zhang JF, Ning JF, Wang SF: MicroRNA-378 is associated with non-small cell lung cancer brain metastasis by promoting cell migration, invasion and tumor angiogenesis. Med Oncol 2012; 29: 1673–1680.
Qian J, Lin J, Qian W, Ma JC, Qian SX, Li Y, Yang J, Li JY, Wang CZ, Chai HY, Chen XX, Deng ZQ: Overexpression of miR-378 is frequent and may affect treatment outcomes in patients with acute myeloid leukemia. Leuk Res 2013; 37: 765–768.
Prudkin L, Behrens C, Liu DD, Zhou X, Ozburn NC, Bekele BN, Minna JD, Moran C, Roth JA, Ji L, Wistuba II: Loss and reduction of FUS1 protein expression is a frequent phenomenon in the pathogenesis of lung cancer. Clin Cancer Res 2008; 14: 41–47.
Li G, Kawashima H, Ji L, Ogose A, Ariizumi T, Umezu H, Xu Y, Hotta T, Endo N: Frequent absence of tumor suppressor FUS1 protein expression in human bone and soft tissue sarcomas. Anticancer Res 2011; 31: 11–21.
Xin J, Zhang XK, Xin DY, Li XF, Sun DK, Ma YY, Tian LQ: FUS1 acts as a tumor-suppressor gene by upregulating miR-197 in human glioblastoma. Oncol Rep 2015; 34: 868–876.
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