Low miR‑210 and CASP8AP2 expression is associated with a poor outcome in pediatric acute lymphoblastic leukemia

Mei,Yanyan; Li,Zhigang; Zhang,Yi; Zhang,Weiling; Hu,Huimin; Zhang,Pinwei; Wu,Minyuan; Huang,Dongsheng

doi:10.3892/ol.2017.7229

Low miR‑210 and CASP8AP2 expression is associated with a poor outcome in pediatric acute lymphoblastic leukemia

Authors:
- Yanyan Mei
- Zhigang Li
- Yi Zhang
- Weiling Zhang
- Huimin Hu
- Pinwei Zhang
- Minyuan Wu
- Dongsheng Huang
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Affiliations: Department of Pediatrics, Beijing Tongren Hospital, Capital Medical University, Beijing 100176, P.R. China, Key Laboratory of Major Diseases in Children, Ministry of Education, Department of Hematology, Beijing Children's Hospital, Capital Medical University, Beijing 100045, P.R. China
Published online on: October 20, 2017 https://doi.org/10.3892/ol.2017.7229
Pages: 8072-8077

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Abstract

The prognostic significance of microRNA (miR)‑210 and the caspase 8‑associated protein 2 (CASP8AP2) gene in children with acute lymphoblastic leukemia (ALL) has been validated and CASP8AP2 has been demonstrated as a target of miR‑210. In the present study, the reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) was used to determine miR‑210 and CASP8AP2 expression in 91 children with ALL. Associations between gene expression levels and the prognostic value of combined detection of the two indicators were analyzed. Results from a receiver operating characteristic curve demonstrated that threshold values of miR‑210 and CASP8AP2 were 3.8243 and 0.4760, respectively. Although the expression of miR‑210 and CASP8AP2 were not associated at the mRNA level in pediatric ALL, combined detection of the two predicted ALL prognosis with an increased accuracy. Furthermore, an equation was devised including minimal residual disease at day 33 and expression of miR‑210 and CASP8AP2, which may enable bone marrow relapse to be predicted more precisely compared with the current risk stratification.

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1	Pui CH, Carroll WL, Meshinchi S and Arceci RJ: Biology, risk stratification, and therapy of pediatric acute leukemias: An update. J Clin Oncol. 29:551–565. 2011. View Article : Google Scholar : PubMed/NCBI
2	Hunger SP, Lu X, Devidas M, Camitta BM, Gaynon PS, Winick NJ, Reaman GH and Carroll WL: Improved survival for children and adolescents with acute lymphoblastic leukemia between 1990 and 2005: A report from the children's oncology group. J Clin Oncol. 30:1663–1669. 2012. View Article : Google Scholar : PubMed/NCBI
3	Locatelli F, Schrappe M, Bernardo ME and Rutella S: How I treat relapsed childhood acute lymphoblastic leukemia. Blood. 120:2807–2816. 2012. View Article : Google Scholar : PubMed/NCBI
4	Bhojwani D and Pui CH: Relapsed childhood acute lymphoblastic leukaemia. Lancet Oncol. 14:e205–e217. 2013. View Article : Google Scholar : PubMed/NCBI
5	Pui CH, Mullighan CG, Evans WE and Relling MV: Pediatric acute lymphoblastic leukemia: Where are we going and how do we get there? Blood. 120:1165–1174. 2012. View Article : Google Scholar : PubMed/NCBI
6	Huang X, Le QT and Giaccia AJ: MiR-210-micromanager of the hypoxia pathway. Trends Mol Med. 16:230–237. 2010. View Article : Google Scholar : PubMed/NCBI
7	Devlin C, Greco S, Martelli F and Ivan M: miR-210: More than a silent player in hypoxia. IUBMB Life. 63:94–100. 2011.PubMed/NCBI
8	Crosby ME, Kulshreshtha R, Ivan M and Glazer PM: MicroRNA regulation of DNA repair gene expression in hypoxic stress. Cancer Res. 69:1221–1229. 2009. View Article : Google Scholar : PubMed/NCBI
9	Chan SY and Loscalzo J: MicroRNA-210: A unique and pleiotropic hypoxamir. Cell Cycle. 9:1072–1083. 2010. View Article : Google Scholar : PubMed/NCBI
10	Mei Y, Gao C, Wang K, Cui L, Li W, Zhao X, Liu F, Wu M, Deng G, Ding W, et al: Effect of microRNA-210 in prognosis and response to chemotherapeutic drugs in pediatric acute lymphoblastic leukemia. Cancer Sci. 105:463–472. 2014. View Article : Google Scholar : PubMed/NCBI
11	Barcaroli D, Dinsdale D, Neale MH, Bongiorno-Borbone L, Ranalli M, Munarriz E, Sayan AE, McWilliam JM, Smith TM, Fava E, et al: FLASH is an essential component of Cajal bodies. Proc Natl Acad Sci USA. 103:pp. 14802–14807. 2006, View Article : Google Scholar : PubMed/NCBI
12	Barcaroli D, Bongiorno-Borbone L, Terrinoni A, Hofmann TG, Rossi M, Knight RA, Matera AG, Melino G and De Laurenzi V: FLASH is required for histone transcription and S-phase progression. Proc Natl Acad Sci USA. 103:pp. 14808–14812. 2006, View Article : Google Scholar : PubMed/NCBI
13	Chen S, Evans HG and Evans DR: FLASH knockdown sensitizes cells to Fas-mediated apoptosis via down-regulation of the anti-apoptotic proteins, MCL-1 and Cflip short. PLoS One. 7:e329712012. View Article : Google Scholar : PubMed/NCBI
14	Flotho C, Coustan-Smith E, Pei D, Iwamoto S, Song G, Cheng C, Pui CH, Downing JR and Campana D: Genes contributing to minimal residual disease in childhood acute lymphoblastic leukemia: Prognostic significance of CASP8AP2. Blood. 108:1050–1057. 2006. View Article : Google Scholar : PubMed/NCBI
15	Kim HW, Haider HK, Jiang S and Ashraf M: Ischemic preconditioning augments survival of stem cells via miR-210 expression by targeting caspase-8-associated protein 2. J Biol Chem. 284:33161–33168. 2009. View Article : Google Scholar : PubMed/NCBI
16	Carroll WL, Bhojwani D, Min DJ, Raetz E, Relling M, Davies S, Downing JR, Willman CL and Reed JC: Pediatric acute lymphoblastic leukemia. Hematology Am Soc Hematol Educ Program. 102–131. 2003.PubMed/NCBI
17	Wang KL, Mei YY, Cui L, Zhao XX, Li WJ, Gao C, Liu SG, Jiao Y, Liu FF, Wu MY, et al: E2F3a gene expression has prognostic significance in childhood acute lymphoblastic leukemia. Eur J Haematol. 93:281–289. 2014. View Article : Google Scholar : PubMed/NCBI
18	Rieu I and Powers SJ: Real-time quantitative RT-PCR: Design, calculations, and statistics. Plant Cell. 21:1031–1033. 2009. View Article : Google Scholar : PubMed/NCBI
19	Pallisgaard N, Clausen N, Schroder H and Hokland P: Rapid and sensitive minimal residual disease detection in acute leukemia by quantitative real-time RT-PCR exemplified by t(12;21) TEL-AML1 fusion transcript. Genes Chromosomes Cancer. 26:355–365. 1999. View Article : Google Scholar : PubMed/NCBI
20	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
21	Gao C, Zhao XX, Li WJ, Cui L, Zhao W, Liu SG, Yue ZX, Jiao Y, Wu MY and Li ZG: Clinical features, early treatment responses, and outcomes of pediatric acute lymphoblastic leukemia in China with or without specific fusion transcripts: A single institutional study of 1,004 patients. Am J Hematol. 87:1022–1027. 2012. View Article : Google Scholar : PubMed/NCBI
22	Mortensen BT, Jensen PO, Helledie N, Iversen PO, Ralfkiaer E, Larsen JK and Madsen MT: Changing bone marrow micro-environment during development of acute myeloid leukaemia in rats. Br J Haematol. 102:458–464. 1998. View Article : Google Scholar : PubMed/NCBI
23	Zhang H, Luo XQ, Zhang P, Huang LB, Zheng YS, Wu J, Zhou H, Qu LH, Xu L and Chen YQ: MicroRNA patterns associated with clinical prognostic parameters and CNS relapse prediction in pediatric acute leukemia. PLoS One. 4:e78262009. View Article : Google Scholar : PubMed/NCBI
24	Qin Q, Furong W and Baosheng L: Multiple functions of hypoxia-regulated miR-210 in cancer. J Exp Clin Cancer Res. 33:502014. View Article : Google Scholar : PubMed/NCBI