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https://doi.org/10.1002/emmm.201202183
Title: | Oncogenic roles of PRL-3 in FLT3-ITD induced acute myeloid leukaemia | Authors: | Park, J.E. Yuen, H.F. Zhou, J.B. Al-aidaroos, A.Q.O. Guo, K. Valk, P.J. Zhang, S.D. Chng, W.J. Hong, C.W. Mills, K. Zeng, Q. |
Keywords: | Acute myeloid leukaemia Antibody therapy FLT3-ITD mutation PRL-3 Prognostic marker |
Issue Date: | Sep-2013 | Citation: | Park, J.E., Yuen, H.F., Zhou, J.B., Al-aidaroos, A.Q.O., Guo, K., Valk, P.J., Zhang, S.D., Chng, W.J., Hong, C.W., Mills, K., Zeng, Q. (2013-09). Oncogenic roles of PRL-3 in FLT3-ITD induced acute myeloid leukaemia. EMBO Molecular Medicine 5 (9) : 1351-1366. ScholarBank@NUS Repository. https://doi.org/10.1002/emmm.201202183 | Abstract: | FLT3-ITD mutations are prevalent mutations in acute myeloid leukaemia (AML). PRL-3, a metastasis-associated phosphatase, is a downstream target of FLT3-ITD. This study investigates the regulation and function of PRL-3 in leukaemia cell lines and AML patients associated with FLT3-ITD mutations. PRL-3 expression is upregulated by the FLT3-STAT5 signalling pathway in leukaemia cells, leading an activation of AP-1 transcription factors via ERK and JNK pathways. PRL-3-depleted AML cells showed a significant decrease in cell growth. Clinically, high PRL-3 mRNA expression was associated with FLT3-ITD mutations in four independent AML datasets with 1158 patients. Multivariable Cox-regression analysis on our Cohort 1 with 221 patients identified PRL-3 as a novel prognostic marker independent of other clinical parameters. Kaplan-Meier analysis showed high PRL-3 mRNA expression was significantly associated with poorer survival among 491 patients with normal karyotype. Targeting PRL-3 reversed the oncogenic effects in FLT3-ITD AML models in vitro and in vivo. Herein, we suggest that PRL-3 could serve as a prognostic marker to predict poorer survival and as a promising novel therapeutic target for AML patients. © 2013 The Authors. Published by John Wiley and Sons, Ltd on behalf of EMBO. | Source Title: | EMBO Molecular Medicine | URI: | http://scholarbank.nus.edu.sg/handle/10635/117106 | ISSN: | 17574676 | DOI: | 10.1002/emmm.201202183 |
Appears in Collections: | Staff Publications |
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