Background: Acute lymphoblastic leukemia (ALL), a common pediatric malignant neoplasia, showed high relapse rate after induction therapy. Some miRNAs have been shown to regulate normal hematopoiesis and their disruption could contribute to leukemogenesis: Recently, specific miRNA, including miR-181a, was shown to be involved in the pathogenesis of ALL, serving as a biomarker for diagnosis and relapse of ALL. Aim of the Study : To evaluate miR-181a expression level as a predictive marker for children with acute lymphoblastic leukemia. Patients and Methods : 40 pediatric ALL patients were included in this study. miR-181a expression was assessed at diagnosis before start of treatment. Samples were either peripheral blood or bone marrow aspirate sample. Patients were evaluated clinically and laboratory after the induction therapy. Results : The remission rate was significantly higher in patients with high miR-181a expression compared to those with low expression (p < 0.001). Conclusion : The expression level of miR-181a was significantly higher in remission group than in non-remission group was and predict good response to induction therapy .
KeywordsmiR-181aMicro-RNAALL
Pui, C.H. (2010) Recent Research Advances in Childhood Acute Lymphoblastic Leukemia. Journal of the Formosan Medical Association, 109, 777-787. https://doi.org/10.1016/S0929-6646(10)60123-4
Coustan-Smith, E., Song, G., Clark, C., Key, L., Liu, P., Mehrpooya, M., Stow, P., Su, X., Shurtleff, S., Pui, C.H., Downing, J.R. and Campana, D. (2011) New Markers for Minimal Residual Disease Detection in Acute Lymphoblastic Leukemia. Blood, 117, 6267-6276. https://doi.org/10.1182/blood-2010-12-324004
Zhou, X., Wen, W., Shan, X., Zhu, W., Xu, J., Guo, R., Cheng, W., Wang, F., Qi, L.W., Chen, Y., Huang, Z., Wang, T., Zhu, D., Liu, P. and Shu, Y. (2017) A Six-microRNA Panel in Plasma Was Identified as a Potential Biomarker for Lung Adenocarcinoma Diagnosis. Oncotarget, 8, 6513-6525. https://doi.org/10.18632/oncotarget.14311
Tombak, A., Gorur, A., Balci, S., Tiftik, N. and Tamer, L. (2015) Circulating microRNAs in Newly Diagnosed Acute and Chronic Leukemias. International Journal of Hematology and Oncology, 25, 75-80.
Li, X.J., Luo, X.Q., Han, B.W., Duan, F.T., Wei, P.P. and Chen, Y.Q. (2013) MicroRNA-100/99a, Deregulated in Acute Lymphoblastic Leukaemia, Suppress Proliferation and Promote Apoptosis by Regulating the FKBP51 and IGF1R/mTOR Signalling Pathways. British Journal of Cancer, 109, 2189-2198. https://doi.org/10.1038/bjc.2013.562
Yan, J., Jiang, N., Huang, G., Tay, J.L., Lin, B., Bi, C., Koh, G.S., Li, Z., Tan, J., Chung, T.H., Lu, Y., Ariffin, H., Kham, S.K., Yeoh, A.E. and Chng, W.J. (2013) Deregulated MIR335 That Targets MAPK1 Is Implicated in Poor Outcome of Paediatric Acute Lymphoblastic Leukaemia. British Journal of Haematology, 163, 93-103. https://doi.org/10.1111/bjh.12489
Burke, M.J. and Bhatla, T. (2014) Epigenetic Modifications in Pediatric Acute Lymphoblastic Leukemia. Frontiers in Pediatrics, 2, 42. https://doi.org/10.3389/fped.2014.00042
Li, W.Y., Chen, X.M., Xiong, W., Guo, D.M., Lu, L. and Li, H.Y. (2014) Detection of Microvesicle miRNA Expression in ALL Subtypes and Analysis of Their Functional Roles. Journal of Huazhong University of Science and Technology (Medical Science), 34, 640-645. https://doi.org/10.1007/s11596-014-1330-0
de Oliveira, J.C., Scrideli, C.A., Brassesco, M.S., Morales, A.G., Pezuk, J.A., Queiroz Rde, P., Yunes, J.A., Brandalise, S.R. and Tone, L.G. (2012) Differential miRNA Expression in Childhood Acute Lymphoblastic Leukemia and Association with Clinical and Biological Features. Leukemia Research, 36, 293-298. https://doi.org/10.1016/j.leukres.2011.10.005
Belkaya, S., Silge, R.L., Hoover, A.R., Medeiros, J.J., Eitson, J.L., Becker, A.M., de la Morena, M.T., Bassel-Duby, R.S. and van Oers, N.S. (2011) Dynamic Modulation of Thymic microRNAs in Response to Stress. PLoS ONE, 6, e27580. https://doi.org/10.1371/journal.pone.0027580
Neilson, J.R., Zheng, G.X., Burge, C.B. and Sharp, P.A. (2007) Dynamic Regulation of miRNA Expression in Ordered Stages of Cellular Development. Genes & Development, 21, 578-589. https://doi.org/10.1101/gad.1522907
Duyu, M., Durmaz, B., Gunduz, C., Vergin, C., Yilmaz Karapinar, D., Aksoylar, S., Kavakli, K., Cetingul, N., Irken, G., Yaman, Y., Ozkinay, F. and Cogulu, O. (2014) Prospective Evaluation of Whole Genome microRNA Expression Profiling in Childhood Acute Lymphoblastic Leukemia. BioMed Research International, 2014, Article ID: 967585. https://doi.org/10.1155/2014/967585
El-Khazragy, N., Noshi, M.A., Abdel-Malak, C., Zahran, R.F. and Swellam, M. (2019) miRNA-155 and miRNA-181a as Prognostic Biomarkers for Pediatric Acute Lymphoblastic Leukemia. Journal of Cellular Biochemistry, 120, 6315-6321. https://doi.org/10.1002/jcb.27918
Yan, Z.X., Zheng, Z., Xue, W., Zhao, M.Z., Fei, X.C., Wu, L.L., Huang, L.M., Leboeuf, C., Janin, A., Wang, L. and Zhao, W.L. (2015) MicroRNA181a Is Overexpressed in T-Cell Leukemia/Lymphoma and Related to Chemoresistance. BioMed Research International, 2015, Article ID: 197241. https://doi.org/10.1155/2015/197241
Wang, J.J. and Yu, J.P. (2019) miR-181a Down-Regulates MAP2K1 to Enhance Adriamycin Sensitivity in Leukemia HL-60 Cells. European Review for Medical and Pharmacological Sciences, 23, 2497-2504.
Lin, S., Pan, L., Guo, S., Wu, J., Jin, L., Wang, J.C. and Wang, S. (2013) Prognostic Role of microRNA-181a/b in Hematological Malignancies: A Meta-Analysis. PLoS ONE, 8, e59532. https://doi.org/10.1371/journal.pone.0059532
Li, H., Hui, L. and Xu, W. (2012) miR-181a Sensitizes a Multidrug-Resistant Leukemia Cell Line K562/A02 to Daunorubicin by Targeting BCL-2. Acta Biochimica et Biophysica Sinica (Shanghai), 44, 269-277. https://doi.org/10.1093/abbs/gmr128
Bai, H., Cao, Z., Deng, C., Zhou, L. and Wang, C. (2012) miR-181a Sensitizes Resistant Leukaemia HL-60/Ara-C Cells to Ara-C by Inducing Apoptosis. Journal of Cancer Research and Clinical Oncology, 138, 595-602. https://doi.org/10.1007/s00432-011-1137-3
Zhu, Y.D., Wang, L., Sun, C., Fan, L., Zhu, D.X., Fang, C., Wang, Y.H., Zou, Z.J., Zhang, S.J., Li, J.Y. and Xu, W. (2012) Distinctive microRNA Signature Is Associated with the Diagnosis and Prognosis of Acute Leukemia. Medical Oncology, 29, 2323-2331. https://doi.org/10.1007/s12032-011-0140-5
Han, B.W., Feng, D.D., Li, Z.G., Luo, X.Q., Zhang, H., Li, X.J., Zhang, X.J., Zheng, L.L., Zeng, C.W., Lin, K.Y., Zhang, P., Xu, L. and Chen, Y.Q. (2011) A Set of miRNAs That Involve in the Pathways of Drug Resistance and Leukemic Stem-Cell Differentiation Is Associated with the Risk of Relapse and Glucocorticoid Response in Childhood ALL. Human Molecular Genetics, 20, 4903-4915. https://doi.org/10.1093/hmg/ddr428
Wang, Y., Li, Z., He, C., Wang, D., Yuan, X., Chen, J. and Jin, J. (2010) MicroRNAs Expression Signatures Are Associated with Lineage and Survival in Acute Leukemias. Blood Cells, Molecules and Diseases, 44, 191-197. https://doi.org/10.1016/j.bcmd.2009.12.010