title: High expression of S100A8 gene is associated with drug resistance to etoposide and poor prognosis in acute myeloid leukemia through influencing the apoptosis pathway.
abstract: S100A8 has been increasingly recognized as a biomarker in multiple solid tumors and has played pivotal roles in hematological malignancies. S100A8 is potentially an indicator for poor survival in acute myeloid leukemia (AML) in retrospective studies. However, the mechanisms of S100A8 are diverse in cancers. In this study, we investigated the correlation of S100A8 at the transcription level with clinical parameters in 91 de novo AML patients and explored its mechanisms of chemoresistance to etoposide in vitro. The transcription level of S100A8 was significantly lower at initial and relapse stages of AML samples than at complete remission (P<0.001) and than in the control group (P=0.0078), while no significant difference could be found between initial and relapse stages (P=0.257). Patients with high transcription levels of S100A8 exhibited a shorter overall survival (P=0.0012). HL-60 cells transfected with S100A8 showed resistance to etoposide with a higher level IC50 value and lower apoptosis rate compared with HL-60 cells transfected with empty vector. Thirty-six genes were significantly downregulated and 12 genes were significantly upregulated in S100A8 overexpression group compared with control group in which 360 genes involved in apoptotic genes array were performed by real-time reverse transcriptase polymerase chain reaction. Among them, the caspase-3, Bcl-2, and Bax were verified by Western blot analysis which indicated that the role of S100A8 in resistance to chemotherapy was closely related with antiapoptosis. In conclusion, critical S100A8 provided useful clinical information in predicting the outcome of AML. The main mechanism of S100A8 which promoted chemoresistance was antiapoptosis.
authors.affiliation: Department of Haematology and Oncology, Children's Hospital of Soochow University.
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Yang
authors.affiliation: Department of Haematology and Oncology, Children's Hospital of Soochow University.
authors.forename: Ming-Ying
authors.initials: MY
authors.lastname: Zhang
authors.affiliation: Department of Haematology and Oncology, Children's Hospital of Soochow University.
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: Department of Haematology and Oncology, Children's Hospital of Soochow University.
authors.forename: Shui-Yan
authors.initials: SY
authors.lastname: Wu
authors.affiliation: Department of Haematology, The First Affiliated Hospital of Soochow University, Suzhou.
authors.forename: Ye
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Haematology, The Third Affiliated Hospital of Soochow University, Changzhou, People's Republic of China.
authors.forename: Wei-Ying
authors.initials: WY
authors.lastname: Gu
authors.affiliation: Department of Haematology and Oncology, Children's Hospital of Soochow University.
authors.forename: Jian
authors.initials: J
authors.lastname: Pan
authors.affiliation: Department of Haematology, The First Affiliated Hospital of Soochow University, Suzhou.
authors.forename: Jian-Nong
authors.initials: JN
authors.lastname: Cen
authors.affiliation: Department of Haematology, The First Affiliated Hospital of Soochow University, Suzhou.
authors.forename: Zi-Xing
authors.initials: ZX
authors.lastname: Chen
authors.affiliation: Department of Mathematical Sciences, New Jersey Institute of Technology, Newark, NJ.
authors.forename: Wen-Ge
authors.initials: WG
authors.lastname: Guo
authors.affiliation: Department of Internal Medicine, Division of Hematology and Medical Oncology and Biospecimen Laboratory, Loma Linda University, Loma Linda, CA, USA.
authors.forename: Chien-Shing
authors.initials: CS
authors.lastname: Chen
authors.affiliation: Department of Cardiology, Children's Hospital of Soochow University, Suzhou, People's Republic of China.
authors.forename: Wen-Hua
authors.initials: WH
authors.lastname: Yan
authors.affiliation: Department of Haematology and Oncology, Children's Hospital of Soochow University.
authors.forename: Shao-Yan
authors.initials: SY
authors.lastname: Hu
keywords: AML; HL-60 cell; S100A8; acute myeloid leukemia; antiapoptosis; drug resistance; overall survival; prognostic factor