Department of Pathology and Immunology, Washington University in St. Louis, United States.
Semin Cancer Biol. 2014 Aug;27:3-10. doi: 10.1016/j.semcancer.2014.02.009. Epub 2014 Mar 18.
Hematologic malignancies are often associated with chromosomal rearrangements that lead to the expression of chimeric fusion proteins. Rearrangements of the genes encoding two nucleoporins, NUP98 and NUP214, have been implicated in the pathogenesis of several types of hematologic malignancies, particularly acute myeloid leukemia. NUP98 rearrangements result in fusion of an N-terminal portion of NUP98 to one of numerous proteins. These rearrangements often follow treatment with topoisomerase II inhibitors and tend to occur in younger patients. They have been shown to induce leukemia in mice and to enhance proliferation and disrupt differentiation in primary human hematopoietic precursors. NUP214 has only a few fusion partners. DEK-NUP214 is the most common NUP214 fusion in AML; it tends to occur in younger patients and is usually associated with FLT3 internal tandem duplications. The leukemogenic activity of NUP214 fusions is less well characterized. Normal nucleoporins, including NUP98 and NUP214, have important functions in nucleocytoplasmic transport, transcription, and mitosis. These functions and their disruptions by oncogenic nucleoporin fusions are discussed.
血液系统恶性肿瘤常与染色体重排有关，这些重排导致嵌合融合蛋白的表达。编码两个核孔蛋白 NUP98 和 NUP214 的基因重排与多种血液系统恶性肿瘤的发病机制有关，尤其是急性髓系白血病。NUP98 重排导致 NUP98 的 N 端部分与许多蛋白质之一融合。这些重排通常在拓扑异构酶 II 抑制剂治疗后发生，并且往往发生在年轻患者中。它们已被证明可以在小鼠中诱导白血病，并增强原代人类造血前体细胞的增殖和分化。NUP214 只有少数融合伙伴。DEK-NUP214 是 AML 中最常见的 NUP214 融合；它往往发生在年轻患者中，通常与 FLT3 内部串联重复有关。NUP214 融合的致白血病活性尚未得到很好的描述。正常核孔蛋白，包括 NUP98 和 NUP214，在核质转运、转录和有丝分裂中具有重要功能。讨论了这些功能及其被致癌核孔蛋白融合破坏的情况。
