title: Homoharringtonine combined with aclarubicin and cytarabine synergistically induces apoptosis in t(8;21) leukemia cells and triggers caspase-3-mediated cleavage of the AML1-ETO oncoprotein.
abstract: Homoharringtonine combined with aclarubicin and cytarabine (HAA) is a highly effective treatment for acute myeloid leukemia (AML), especially for t(8;21) AML. However, the underlying mechanisms by which HAA kills t(8;21) AML cells remain unclear. In this study, SKNO-1 and Kasumi-1 cells with t(8;21) were used. Compared with individual or pairwise administration of homoharringtonine, aclarubicin, or cytarabine, HAA showed the strongest inhibition of growth and induction of apoptosis in SKNO-1 and Kasumi-1 cells. HAA caused cleavage of the AML1-ETO (AE) oncoprotein to form truncated AE (ΔAE). Pretreatment with the caspase-3 inhibitor caspase-3 inhibitor Q-DEVD-OPh (QDO) not only suppressed HAA-induced apoptosis but also abrogated the cleavage of AE and generation of ΔAE. These results suggest that HAA synergistically induces apoptosis in t(8;21) leukemia cells and triggers caspase-3-mediated cleavage of the AML1-ETO oncoprotein, thus providing direct evidence for the strong activity of HAA toward t(8;21) AML.
authors.affiliation: Department of Hematology, The Affiliated Hospital of Xuzhou Medical College, XuZhou, 221002, China.
authors.forename: Jiang
authors.initials: J
authors.lastname: Cao
authors.affiliation: Department of Hematology, The Affiliated Hospital of Xuzhou Medical College, XuZhou, 221002, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Feng
authors.affiliation: Department of Hematology, The Affiliated Hospital of Xuzhou Medical College, XuZhou, 221002, China.
authors.forename: Ning-Ning
authors.initials: NN
authors.lastname: Ding
authors.affiliation: Department of Hematology, The Affiliated Hospital of Xuzhou Medical College, XuZhou, 221002, China.
authors.forename: Qing-Yun
authors.initials: QY
authors.lastname: Wu
authors.affiliation: Department of Hematology, The Affiliated Hospital of Xuzhou Medical College, XuZhou, 221002, China.
authors.forename: Chong
authors.initials: C
authors.lastname: Chen
authors.affiliation: Department of Hematology, The Affiliated Hospital of Xuzhou Medical College, XuZhou, 221002, China.
authors.forename: Ming-Shan
authors.initials: MS
authors.lastname: Niu
authors.affiliation: Department of Hematology, The Affiliated Hospital of Xuzhou Medical College, XuZhou, 221002, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Hematology, The Affiliated Hospital of Xuzhou Medical College, XuZhou, 221002, China.
authors.forename: Ting-Ting
authors.initials: TT
authors.lastname: Qiu
authors.affiliation: Department of Hematology, Peking University People's Hospital, Beijing, 100044, China.
authors.forename: Hong-Hu
authors.initials: HH
authors.lastname: Zhu
authors.affiliation: Department of Hematology, The Affiliated Hospital of Xuzhou Medical College, XuZhou, 221002, China.
authors.forename: Kai-Lin
authors.initials: KL
authors.lastname: Xu
mesh_terms: D015250:Aclarubicin / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002891:Chromosomes, Human, Pair 21; D002898:Chromosomes, Human, Pair 8; D050676:Core Binding Factor Alpha 2 Subunit / Q000378:metabolism*; D003561:Cytarabine / Q000494:pharmacology*; D004357:Drug Synergism; D006248:Harringtonines / Q000494:pharmacology*; D000077863:Homoharringtonine; D006801:Humans; D007938:Leukemia; D015514:Oncogene Proteins, Fusion / Q000378:metabolism*; D059748:Proteolysis / Q000187:drug effects; D000075142:RUNX1 Translocation Partner 1 Protein / Q000378:metabolism*; D014178:Translocation, Genetic
chemical_list: C107844:AML1-ETO fusion protein, human; D000970:Antineoplastic Agents; D050676:Core Binding Factor Alpha 2 Subunit; D006248:Harringtonines; D015514:Oncogene Proteins, Fusion; D000075142:RUNX1 Translocation Partner 1 Protein; D003561:Cytarabine; D000077863:Homoharringtonine; D015250:Aclarubicin; D053148:Caspase 3
keywords: AML1-ETO; Acute myeloid leukemia; homoharringtonine combined with aclarubicin and cytarabine; synergistic