Expression Level Of SET Gene In De Novo Adult Acute Myeloid Leukemia And Its Clinical Significance

Background and objective:Adult acute myeloid leukemia (AML) is a group of malignant tumors and its pathogenesis remains unclear. Though the diagnosis and treatment technology have improved, its long survival remains poor. Therefore, the first step of improving survival is to better the evaluation system for prognosis and find new molecular targets. Our study is to examine the expression level of SET gene in de novo AML patients, study the relationship between FLT3-ITD, NPMl gene mutations and SET gene expression, and explore the correlation of SET gene expression level with adult AML patients clinical features and prognosis.Methods:1. Bone marrows (BM) samples were collected from de novo adult AML patients and nomal control;2. Stable and reliable RQ-PCR method was used to detect SET gene expressions in AML patients; and we identified mutations of NPMl and FLT3using PCR combined with Snager sequencing.3.These AML patients were divided into some groups according SET gene expression, and the clinical features and prognosis of AML patients were analyzed by statistical software of SPSS-16.Results:1.In all141de novo adult AML patients, FLT3-ITD and NPM1gene mutations were examined in104patients, SET gene expression was detected in141examples.2.1n a total of104patients,77cases harbored normal karyotype.[8(7.7%) patients had NPM1+/FLT3-ITD+,16(15.4%) patients had NPM1+/FLT3-ITD-,12(11.5%) patients had NPM1-/FLT3-ITD+,68(65.4%) patients had NPM1-/FLT3-ITD-].3.The clinical relevance and prognostic significance of SET gene expression in AML.3.1The SET gene transcript levels were detected in141de novo AML patients and10healthy donors and SET gene expression levels in healthy donors (median:0.21, range:0.05-0.43) were significantly lower than those in de novo AML pathients (median:0.86, range:0.02-l5.69, P＜0.001).3.2SET gene expression level was not correlated with age, sex, hemoglobin level, platelet count, bone marrow blast cells, FAB classification, chromosome karyotype, NPMl and FLT3-ITD gene mutations(all P>0.05), but higher SET expression group had higher rate of WBC≥100xl09/L patients than lower SET expression group (31.0%vs11.4%,P=0.005), and SET gene expression level was higher in WBC≥100xl09/L group than WBC<100xl09/L group(1.08vs0.82, P=0.012).3.3SET gene expression was examinated in10patients with complete remission (CR), the expression level of SET gene was obviously decreased (19.2%-80.0%) when CR was achieved (P=0.002).3.4In the whole population with chemotherapy treatment (136patients), young patients (age<60years), who were not obtained the CR harbored the higher level of SET gene expression(all P<0.05).3.5Patients with SET overexpression had poor overall survival (OS)(P<0.05) and event-free survival (EFS)(P<0.05).3.6Multivariate COX regression analysis showed SET overexpression was an independent prognostic factor for OS in the whole population and young patients (all P<0.05), and an independent prognostic factor for OS and EFS in cytogenetically normal acute myeloid leukemia (CN-AML)(all P<0.05).Conclusion:l.SET gene expression level is higher in de novo acute AML than in nomal control and those patients with CR.2. The SET gene overexpression is positively related with the high white blood cell and non-remission.3.SET gene overexpression is an independently adverse factor for prognosis of adult AML patients.