The hypomethylating agent decitabine prior to chemotherapy improves the therapy efficacy in refractory/relapsed acute myeloid leukemia patients
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Xuejie Jiang1, Zhixiang Wang1, Bingjie Ding1, Changxin Yin1, Qingxiu Zhong1,2, Bing Z. Carter3, Guopan Yu1, Ling Jiang1, Jieyu Ye1, Min Dai1, Yu Zhang1, Shuang Liang4, Qingxia Zhao5, Qifa Liu1 and Fanyi Meng1,2
1 Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, China
2 Hematopathy Diagnosis and Therapy Center, Kanghua Hospital, Dongguan, China
3 Section of Molecular Hematology and Therapy, Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
4 Southern Medical University, Guangzhou, China
5 Department of Stomatology, Nanfang Hospital, Southern Medical University, Guangzhou, China
Fanyi Meng, email:
Keywords: hypomenthylating agent, decitabine, refractory, relapse, AML
Received: March 16, 2015 Accepted: August 26, 2015 Published: September 10, 2015
In this study, we investigated the effect of pre-treatment with demethylating agent decitabine on susceptibility to chemotherapeutic drugs in HL60/ADR, Kasumi-1 and primary AML cells. Cytotoxic effect was increased by decitabine through activation of p53 and inhibition of c-Myc, Survivin and Bcl-2. We demonstrated in clinic that combination of decitabine and HAA consisting of harringtonine, aclarubicin and cytarabine was effective and safe to treat patients with refractory, relapsed or high-risk AML. Decitabine prior to HAA regimen improved the first induction complete response rate, and significantly prolonged overall survival and disease-free survival in these patients compared with HAA alone. These findings support clinic protocols based on decitabine prior to chemotherapy to overcome resistance and improve therapeutic efficacy in AML patients.
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