title: Low expressions of ARS2 and CASP8AP2 predict relapse and poor prognosis in pediatric acute lymphoblastic leukemia patients treated on China CCLG-ALL 2008 protocol.
abstract: ARS2 protein is important to early development and cell proliferation, in which ARS2-CASP8AP2 interaction is implicated. However, the predictive significance of ARS2 in childhood acute lymphoblastic leukemia (ALL) is unknown. Here we evaluate the predictive values of ARS2 expression and combined ARS2 and CASP8AP2 expression in relapse. We showed that ARS2 expression in ALL bone marrow samples at initial diagnosis was markedly lower than that in complete remission (CR). Likewise, the levels of ARS2 expression in the patients suffering from relapse were significantly lower than that of patients in continuous CR. Furthermore, low expression of ARS2 was closely correlated to poor treatment response including poor prednisone response and high minimal residual disease (MRD), and the patients with high MRD (≥10(-4)) and low ARS2 were more subject to relapse. The multivariate analyses for relapse free survival and event free survival revealed that ARS2 expression remained an independent prognostic factor after adjusting other risk factors. In addition, combined assessment of ARS2 and CASP8AP2 expression was more accurate to predict relapse, based on which an algorithm composed of ARS2 and CASP8AP2 expression, prednisone response and MRD (day 78) was proposed. Together, ARS2 and CASP8AP2 expressions can precisely predict high-risk of relapse and ALL prognosis.
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Capital Medical University, Beijing, China; Beijing Key Laboratory of Pediatric Hematology Oncology, National Key Discipline of Pediatrics, Ministry of Education, Key Laboratory of Major Diseases in Children, Ministry of Education, Hematology Oncology Center, Beijing Children's Hospital, Capital Medical University, Beijing, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Cui
authors.affiliation: Beijing Key Laboratory of Pediatric Hematology Oncology, National Key Discipline of Pediatrics, Ministry of Education, Key Laboratory of Major Diseases in Children, Ministry of Education, Hematology Oncology Center, Beijing Children's Hospital, Capital Medical University, Beijing, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Gao
authors.affiliation: Beijing Key Laboratory of Pediatric Hematology Oncology, National Key Discipline of Pediatrics, Ministry of Education, Key Laboratory of Major Diseases in Children, Ministry of Education, Hematology Oncology Center, Beijing Children's Hospital, Capital Medical University, Beijing, China.
authors.forename: Rui-Dong
authors.initials: RD
authors.lastname: Zhang
authors.affiliation: Beijing Key Laboratory of Pediatric Hematology Oncology, National Key Discipline of Pediatrics, Ministry of Education, Key Laboratory of Major Diseases in Children, Ministry of Education, Hematology Oncology Center, Beijing Children's Hospital, Capital Medical University, Beijing, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Jiao
authors.affiliation: Beijing Key Laboratory of Pediatric Hematology Oncology, National Key Discipline of Pediatrics, Ministry of Education, Key Laboratory of Major Diseases in Children, Ministry of Education, Hematology Oncology Center, Beijing Children's Hospital, Capital Medical University, Beijing, China.
authors.forename: Wei-Jing
authors.initials: WJ
authors.lastname: Li
authors.affiliation: Beijing Key Laboratory of Pediatric Hematology Oncology, National Key Discipline of Pediatrics, Ministry of Education, Key Laboratory of Major Diseases in Children, Ministry of Education, Hematology Oncology Center, Beijing Children's Hospital, Capital Medical University, Beijing, China.
authors.forename: Xiao-Xi
authors.initials: XX
authors.lastname: Zhao
authors.affiliation: Beijing Key Laboratory of Pediatric Hematology Oncology, National Key Discipline of Pediatrics, Ministry of Education, Key Laboratory of Major Diseases in Children, Ministry of Education, Hematology Oncology Center, Beijing Children's Hospital, Capital Medical University, Beijing, China.
authors.forename: Shu-Guang
authors.initials: SG
authors.lastname: Liu
authors.affiliation: Beijing Key Laboratory of Pediatric Hematology Oncology, National Key Discipline of Pediatrics, Ministry of Education, Key Laboratory of Major Diseases in Children, Ministry of Education, Hematology Oncology Center, Beijing Children's Hospital, Capital Medical University, Beijing, China.
authors.forename: Zhi-Xia
authors.initials: ZX
authors.lastname: Yue
authors.affiliation: Beijing Key Laboratory of Pediatric Hematology Oncology, National Key Discipline of Pediatrics, Ministry of Education, Key Laboratory of Major Diseases in Children, Ministry of Education, Hematology Oncology Center, Beijing Children's Hospital, Capital Medical University, Beijing, China.
authors.forename: Hu-Yong
authors.initials: HY
authors.lastname: Zheng
authors.affiliation: Department of Urology, School of Medicine, University of California, San Francisco, CA, USA.
authors.forename: Guo-Ren
authors.initials: GR
authors.lastname: Deng
authors.affiliation: Beijing Key Laboratory of Pediatric Hematology Oncology, National Key Discipline of Pediatrics, Ministry of Education, Key Laboratory of Major Diseases in Children, Ministry of Education, Hematology Oncology Center, Beijing Children's Hospital, Capital Medical University, Beijing, China.
authors.forename: Min-Yuan
authors.initials: MY
authors.lastname: Wu
authors.affiliation: Beijing Key Laboratory of Pediatric Hematology Oncology, National Key Discipline of Pediatrics, Ministry of Education, Key Laboratory of Major Diseases in Children, Ministry of Education, Hematology Oncology Center, Beijing Children's Hospital, Capital Medical University, Beijing, China. Electronic address: ericlzg70@gmail.com.
authors.forename: Zhi-Gang
authors.initials: ZG
authors.lastname: Li
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Capital Medical University, Beijing, China. Electronic address: jiahongti@bjmu.edu.cn.
authors.forename: Hong-Ti
authors.initials: HT
authors.lastname: Jia
mesh_terms: D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis*; D002135:Calcium-Binding Proteins / Q000096:biosynthesis*; D002648:Child; D002675:Child, Preschool; D002681:China; D018572:Disease-Free Survival; D005260:Female; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects*; D006801:Humans; D007223:Infant; D008297:Male; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D018365:Neoplasm, Residual; D009687:Nuclear Proteins / Q000096:biosynthesis*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D011237:Predictive Value of Tests; D012008:Recurrence; D015996:Survival Rate
chemical_list: D051017:Apoptosis Regulatory Proteins; C485604:CASP8AP2 protein, human; D002135:Calcium-Binding Proteins; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; C527299:SRRT protein, human
keywords: ARS2; Acute lymphoblastic leukemia; CASP8AP2; Minimal residual disease; Prognosis; Relapse