Please use this identifier to cite or link to this item: https://doi.org/10.1371/journal.pone.0019798
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dc.titlePRL-3, a metastasis associated tyrosine phosphatase, is involved in FLT3-ITD signaling and implicated in anti-aml therapy
dc.contributor.authorZhou, J.
dc.contributor.authorBi, C.
dc.contributor.authorChng, W.-J.
dc.contributor.authorCheong, L.-L.
dc.contributor.authorLiu, S.-C.
dc.contributor.authorMahara, S.
dc.contributor.authorTay, K.-G.
dc.contributor.authorZeng, Q.
dc.contributor.authorLi, J.
dc.contributor.authorGuo, K.
dc.contributor.authorTan, C.P.B.
dc.contributor.authorYu, H.
dc.contributor.authorAlbert, D.H.
dc.contributor.authorChen, C.-S.
dc.date.accessioned2014-12-12T07:12:57Z
dc.date.available2014-12-12T07:12:57Z
dc.date.issued2011
dc.identifier.citationZhou, J., Bi, C., Chng, W.-J., Cheong, L.-L., Liu, S.-C., Mahara, S., Tay, K.-G., Zeng, Q., Li, J., Guo, K., Tan, C.P.B., Yu, H., Albert, D.H., Chen, C.-S. (2011). PRL-3, a metastasis associated tyrosine phosphatase, is involved in FLT3-ITD signaling and implicated in anti-aml therapy. PLoS ONE 6 (5) : -. ScholarBank@NUS Repository. https://doi.org/10.1371/journal.pone.0019798
dc.identifier.issn19326203
dc.identifier.urihttp://scholarbank.nus.edu.sg/handle/10635/115242
dc.description.abstractCombination with other small molecule drugs represents a promising strategy to improve therapeutic efficacy of FLT3 inhibitors in the clinic. We demonstrated that combining ABT-869, a FLT3 inhibitor, with SAHA, a HDAC inhibitor, led to synergistic killing of the AML cells with FLT3 mutations and suppression of colony formation. We identified a core gene signature that is uniquely induced by the combination treatment in 2 different leukemia cell lines. Among these, we showed that downregulation of PTP4A3 (PRL-3) played a role in this synergism. PRL-3 is downstream of FLT3 signaling and ectopic expression of PRL-3 conferred therapeutic resistance through upregulation of STAT (signal transducers and activators of transcription) pathway activity and anti-apoptotic Mcl-1 protein. PRL-3 interacts with HDAC4 and SAHA downregulates PRL-3 via a proteasome dependent pathway. In addition, PRL-3 protein was identified in 47% of AML cases, but was absent in myeloid cells in normal bone marrows. Our results suggest such combination therapies may significantly improve the therapeutic efficacy of FLT3 inhibitors. PRL-3 plays a potential pathological role in AML and it might be a useful therapeutic target in AML, and warrant clinical investigation. © 2011 Zhou et al.
dc.description.urihttp://libproxy1.nus.edu.sg/login?url=http://dx.doi.org/10.1371/journal.pone.0019798
dc.sourceScopus
dc.typeArticle
dc.contributor.departmentCANCER SCIENCE INSTITUTE OF SINGAPORE
dc.contributor.departmentNATIONAL UNIVERSITY MEDICAL INSTITUTES
dc.description.doi10.1371/journal.pone.0019798
dc.description.sourcetitlePLoS ONE
dc.description.volume6
dc.description.issue5
dc.description.page-
dc.identifier.isiut000290531100027
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