Primary mediastinal B-cell lymphoma (PMBL) is a distinct B-cell lymphoma subtype with unique clinicopathological and molecular features. PMBL cells are characterised by several genetic abnormalities that conduct to the constitutive activation of the Janus kinase 2/signal transducer and activator of transcription 6 (JAK2/STAT6) signalling pathway. Among recurrent genetic changes in PMBL, we previously reported that the XPO1 gene encoding exportin 1 that controls the nuclear export of cargo proteins and RNAs, is mutated (p.E571K) in about 25% of PMBL cases. We therefore hypothesized that STAT6 could be a cargo of XPO1 and that STAT6 cytoplasm/nucleus shuttle could be altered in a subset of PMBL cells. Using immunocytochemistry techniques as well as the proximity ligation assay, we showed that STAT6 bound XPO1 in PBML cell lines and in HEK-293 cells genetically engineered to produce STAT6. Moreover, XPO1-mediated export of STAT6 occurs in cells expressing either a wild-type or the E571K mutated XPO1 protein.

原发性纵隔B细胞淋巴瘤（PMBL）是独特的B细胞淋巴瘤亚型，具有独特的临床病理和分子特征。PMBL细胞的特征在于几种遗传异常，这些遗传异常导致Janus激酶2 /信号转导子和转录激活子6（JAK2 / STAT6）信号传导途径的组成性激活。在PMBL的复发性遗传变化中，我们先前曾报道XPO1控制货物蛋白质和RNA核输出的编码exportin 1的基因在大约25％的PMBL病例中发生了突变（p.E571K）。因此，我们假设STAT6可能是XPO1的产物，并且STAT6的细胞质/核穿梭可能会在PMBL细胞子集中发生改变。使用免疫细胞化学技术以及邻近连接测定法，我们表明STAT6结合了PBML细胞系和经基因工程产生STAT6的HEK-293细胞中的XPO1。此外，XPO1介导的STAT6的输出发生在表达野生型或E571K突变的XPO1蛋白的细胞中。