Objective To explore the clinical efficacy of decitabine combined with HAG or HAG-like regimen for newly diagnosed and relapsed/refractory acute myeloid leukemia (AML) patients.Methods Thirty-one newly diagnosed (18 cases) and relapsed/refractory (13 cases) AML patients receiving decitabine combined with HAG or HAG-like regimen in Yinzhou Hospital Affiliated to Medical School of Ningbo University from January 2014 to December 2017 were analyzed retrospectively.Results The outcome of 18 newly diagnosed AML patients showed that the overall response rate (ORR) was 77.8 ％ (14/18),including 13 patients achieved complete response (CR) / CR with incomplete blood count recovery (CRi),and the 1-year overall survival (OS) rate was 39.2 ％,the l-year disease free survival (DFS) rate was 32.5 ％.The outcome of 13 relapsed/refractory AML patients showed that the ORR was 53.8 ％ (7/13),including 6 patients achieved CR/CRi,and the 1-year OS rate was 22.4 ％,the 1-year DFS rate was 7.7 ％.Eleven patients were transformed from myelodysplastic syndromes (MDS),the ORR was 90.9 ％ (10/11),including 9 patients achieved CR/CRi,and the 1-year OS and DFS rates were 63.8 ％ and 37.5 ％ respectively.The main adverse events of infection and bleeding were caused by myelosuppression,and non-hematological toxicity included gastrointestinal and liver dysfunction.After the anti-infection and supportive treatment,all 31 patients were safely through bone marrow suppression,with no treatment-related deaths.Conclusions Decitabine combined with HAG or HAG-like regimen is an effective and safe treatment strategy for hypoplastic newly diagnosed and relapsed/refractory AML patients.It is produced relatively higher curative effect for AML patients with MDS transformation.

OBJECTIVETo investigate the expression level and regulation mechanism of miR-720 as well as the association of miR-720 expression with leukemia biological characteristics.

METHODSExpression and promoter methylation of miR-720 were determined by quantitive PCR and pyrosequencing in 38 patients with AML and 20 normal controls. Lentivirous-mediated miR-702 overexpression was constructed in AML cell line kasumi-1. The cell proliferation, apoptosis, cycle, colony formation, migration and P53-mediated apoptosis pathway were determined.

RESULTSAML patients showed significantly lower miR-720 expression compared with normal controls (0.69±0.09 vs 3.00±0.46, P<0.01); The methylation level of miR-720 promoter region in AML patients were significantly higher than normal controls [(75.56±2.35)% vs (47.65±2.78)%, P<0.01]. miR-720 overexpression in kasumi-1 cells induced significantly increased cell apoptosis (P=0.017), elevated apoptosis sensitivity to etoposide (P=0.004), and reduced cell proliferation (P<0.01). miR-720 overexpression also induced reduced colony formation (P=0.005), cell cycle arrest in G(1)/G(0) phase and decreased migration ability in kasumi-1 cells. In addition, overexpression of miR-720 significantly induced increased cell apoptosis-related proteins including P53 and Bax, and activation of NF-κB signal transduction pathway. After kasumi-1 cells were treated with 1uM decitabine for 48 hours, miR-720 promoter methylation reduced significantly, and miR-720 expression significantly increased.

CONCLUSIONThe expression of miR-720 in AML patients reduced significantly, and DNA methylation-mediated epigenetic silencing of miR-720 contributed to maintain the malignant characteristics of AML.

Apoptosis ; Cell Line, Tumor ; Cell Proliferation ; DNA Methylation ; Epigenesis, Genetic ; Humans ; Leukemia, Myeloid, Acute ; genetics ; pathology ; MicroRNAs ; genetics ; Promoter Regions, Genetic