Cancer Science Institute of Singapore, National University of Singapore, Centre for Translational Medicine, Singapore, Republic of Singapore.
Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Republic of Singapore.
Mol Cancer Res. 2017 Mar;15(3):294-303. doi: 10.1158/1541-7786.MCR-16-0275-T. Epub 2016 Dec 23.
PRL-3 (PTP4A3), a metastasis-associated phosphatase, is also upregulated in patients with acute myeloid leukemia (AML) and is associated with poor prognosis, but the underlying molecular mechanism is unknown. Here, constitutive expression of PRL-3 in human AML cells sustains leukemogenesis and Furthermore, PRL-3 phosphatase activity dependently upregulates LIN28B, a stem cell reprogramming factor, which in turn represses the let-7 mRNA family, inducing a stem cell-like transcriptional program. Notably, elevated levels of LIN28B protein independently associate with worse survival in AML patients. Thus, these results establish a novel signaling axis involving PRL-3/LIN28B/let-7, which confers stem cell-like properties to leukemia cells that is important for leukemogenesis. The current study offers a rationale for targeting PRL-3 as a therapeutic approach for a subset of AML patients with poor prognosis. .
PRL-3（PTP4A3）是一种与转移相关的磷酸酶，在急性髓细胞白血病（AML）患者中也上调，与预后不良相关，但潜在的分子机制尚不清楚。在这里，PRL-3 在人 AML 细胞中的组成性表达维持白血病发生，此外，PRL-3 磷酸酶活性依赖性地上调 LIN28B，一种干细胞重编程因子，反过来又抑制 let-7 mRNA 家族，诱导干细胞样转录程序。值得注意的是，LIN28B 蛋白水平升高与 AML 患者的生存预后不良独立相关。因此，这些结果确立了一个涉及 PRL-3/LIN28B/let-7 的新信号轴，赋予白血病细胞干细胞样特性，这对于白血病发生至关重要。本研究为靶向 PRL-3 作为预后不良的 AML 患者的一种治疗方法提供了依据。
