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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
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.
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
ISSN: 17574676
DOI: 10.1002/emmm.201202183
Appears in Collections:Staff Publications

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