title: The hypomethylating agent decitabine prior to chemotherapy improves the therapy efficacy in refractory/relapsed acute myeloid leukemia patients.
abstract: 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.
authors.affiliation: Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Xuejie
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Zhixiang
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Bingjie
authors.initials: B
authors.lastname: Ding
authors.affiliation: Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Changxin
authors.initials: C
authors.lastname: Yin
authors.affiliation: Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, China.|Hematopathy Diagnosis and Therapy Center, Kanghua Hospital, Dongguan, China.
authors.forename: Qingxiu
authors.initials: Q
authors.lastname: Zhong
authors.affiliation: Section of Molecular Hematology and Therapy, Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Bing Z
authors.initials: BZ
authors.lastname: Carter
authors.affiliation: Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Guopan
authors.initials: G
authors.lastname: Yu
authors.affiliation: Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Jiang
authors.affiliation: Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Jieyu
authors.initials: J
authors.lastname: Ye
authors.affiliation: Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Min
authors.initials: M
authors.lastname: Dai
authors.affiliation: Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Southern Medical University, Guangzhou, China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Liang
authors.affiliation: Department of Stomatology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Qingxia
authors.initials: Q
authors.lastname: Zhao
authors.affiliation: Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Qifa
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, China.|Hematopathy Diagnosis and Therapy Center, Kanghua Hospital, Dongguan, China.
authors.forename: Fanyi
authors.initials: F
authors.lastname: Meng
mesh_terms: D015250:Aclarubicin / Q000008:administration & dosage; D000293:Adolescent; D000328:Adult; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001374:Azacitidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D045744:Cell Line, Tumor; D003561:Cytarabine / Q000008:administration & dosage; D000077209:Decitabine; D018572:Disease-Free Survival; D005260:Female; D018922:HL-60 Cells; D006248:Harringtonines / Q000008:administration & dosage; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000964:Antimetabolites, Antineoplastic; D006248:Harringtonines; D003561:Cytarabine; C062500:harringtonin; D015250:Aclarubicin; D000077209:Decitabine; D001374:Azacitidine
keywords: AML; decitabine; hypomenthylating agent; refractory; relapse