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01.12.2012 | Short communication | Ausgabe 1/2012 Open Access

Molecular Cancer 1/2012

The pro-metastasis tyrosine phosphatase, PRL-3 (PTP4A3), is a novel mediator of oncogenic function of BCR-ABL in human chronic myeloid leukemia

Molecular Cancer > Ausgabe 1/2012
Jianbiao Zhou, Lip-Lee Cheong, Shaw-Cheng Liu, Phyllis SY Chong, Sylvia Mahara, Chonglei Bi, Kelly OK Ong, Qi Zeng, Wee Joo Chng
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1186/​1476-4598-11-72) contains supplementary material, which is available to authorized users.

Competing interests

The authors declare no conflict of interests.

Authors’ contributions

JZ, WJC conceptualized the original idea, designed the experiments and analyzed the data. JZ performed the experiments, wrote the paper. LLC, SCL, PSYC, SM, CB, KOKO contributed to the experiments. QZ provided critical reagents and contributed to discussions and proofread the manuscript. All authors read and approved the final manuscript.



Resistance to tyrosine kinase inhibitors (TKIs) remains a challenge in management of patients with chronic myeloid leukemia (CML). A better understanding of the BCR-ABL signalling network may lead to better therapy.


Here we report the discovery of a novel downstream target of BCR-ABL signalling, PRL-3 (PTP4A3), an oncogenic tyrosine phosphatase. Analysis of CML cancer cell lines and CML patient samples reveals the upregulation of PRL-3. Inhibition of BCR-ABL signalling either by Imatinib or by RNAi silencing BCR-ABL reduces PRL-3 and increases cleavage of PARP. In contrast, the amount of PRL-3 protein remains constant or even increased in response to Imatinib treatment in drug resistant cells expressing P210 T315I. Finally, analysis with specific shRNA shows PRL-3 involvement in the proliferation and self-renewal of CML cells.


These data support a role for PRL-3 in BCR-ABL signalling and CML biology and may be a potential therapeutic target downstream of BCR-ABL in TKI resistant mutant cells.
Additional file 1: Supplementary Methods. (DOC 34 KB)
Additional file 2: Figure Inhibition of MAPK/ERK and PI3K/AKT pathway activities was not correlated to down-regulation of PRL-3 protein level. (A) P210 WT and P210 T315I cells were treated with either vehicle control or various concentrations of Imatinib as indicated for 48 h. Cell lysates were used for Western blot analysis of proteins as indicated. (B) K562 cells were treated with Imatinib 0 (vehicle control), 0.2 and 1 μM for 48 h. Cells were harvested and followed by Western blot analysis of a panel of proteins shown. In both (A) and (B), β-actin was used as a loading control. MOLM-14 cell lysates were used as positive controls for p-AKT antibody. Densitometric analysis was performed using Amersham Image Scanner with LabScan ImageQuant TL Software. (DOC 528 KB)
Authors’ original file for figure 1
Authors’ original file for figure 2
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