Oncogenic roles of PRL‐3 in FLT3‐ITD induced acute myeloid leukaemia. Issue 9 (8th August 2013)

• Record Type: Journal Article
• Authors: Park, Jung Eun; Yuen, Hiu Fung; Zhou, Jian Biao; Al‐aidaroos, Abdul Qader O.; Guo, Ke; Valk, Peter J.; Zhang, Shu Dong; Chng, Wee Joo; Hong, Cheng William; Mills, Ken; Zeng, Qi
• Is Part Of: EMBO molecular medicine. Volume 5:Issue 9(2013:Sep.)
• Page Start: 1351
• Page End: 1366
• Publication Date: 2013-08-08
• Subjects: Molecular biology -- Periodicals; Medical genetics -- Periodicals; Pathology, Molecular -- Periodicals; 616.04205
• DOI: 10.1002/emmm.201202183
• Languages: English
• ISSNs: 1757-4676

Abstract

<abstract abstract-type="main" xml:lang="en"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="emmm201202183-sec-0001" sec-type="section"> <p>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 <italic>in vitro</italic> and <italic>in vivo</italic>. 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.</p> </sec> </abstract>