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PRL3 enhances T-cell acute lymphoblastic leukemia growth through suppressing T-cell signaling pathways and apoptosis.

Leukemia (2020-07-02)
E G Garcia, A Veloso, M L Oliveira, J R Allen, S Loontiens, D Brunson, D Do, C Yan, R Morris, S Iyer, S P Garcia, N Iftimia, W Van Loocke, F Matthijssens, K McCarthy, J T Barata, F Speleman, T Taghon, A Gutierrez, P Van Vlierberghe, W Haas, J S Blackburn, D M Langenau
RESUMEN

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignancy of thymocytes and is largely driven by the NOTCH/MYC pathway. Yet, additional oncogenic drivers are required for transformation. Here, we identify protein tyrosine phosphatase type 4 A3 (PRL3) as a collaborating oncogenic driver in T-ALL. PRL3 is expressed in a large fraction of primary human T-ALLs and is commonly co-amplified with MYC. PRL3 also synergized with MYC to initiate early-onset ALL in transgenic zebrafish and was required for human T-ALL growth and maintenance. Mass-spectrometry phosphoproteomic analysis and mechanistic studies uncovered that PRL3 suppresses downstream T-cell phosphorylation signaling pathways, including those modulated by VAV1, and subsequently suppresses apoptosis in leukemia cells. Taken together, our studies have identified new roles for PRL3 as a collaborating oncogenic driver in human T-ALL and suggest that therapeutic targeting of the PRL3 phosphatase will likely be a useful treatment strategy for T-ALL.

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Sigma-Aldrich
PRL-3 Inhibitor I, ≥98% (HPLC), solid