Laboratory of Cytogenetics and Molecular Genetics, Dmitry Rogachev Research and Clinical Center for Pediatric Hematology, Oncology and Immunology, Moscow, Russia.
Faculty of Fundamental Medicine, Lomonosov Moscow State University, Moscow, Russia.
Genes Chromosomes Cancer. 2018 Oct;57(10):522-524. doi: 10.1002/gcc.22646. Epub 2018 Aug 14.
We present a leukemia case that exhibits a chromosomal translocation t(11;16)(q23;q23), which results in the expression of a novel KMT2A fusion gene. This novel fusion, KMT2A-USP10, was found in a relapse of acute myeloid leukaemia M5a. USP10 belongs to a protein family that deubiquitinates a distinct set of target proteins, and thus, increases the steady state protein levels of its target subproteome. One of the USP10 targets is TP53. Wildtype TP53 is usually rescued from proteasomal degradation by USP10. As most KMT2A leukemias display wildtype p53 alleles, one might argue that the disruption of an USP10 allele can be classified as a pro-oncogenic event.
我们呈现了一例白血病病例，该病例表现出染色体易位 t(11;16)(q23;q23)，导致一种新型 KMT2A 融合基因的表达。这种新型融合基因 KMT2A-USP10 存在于急性髓细胞白血病 M5a 的复发中。USP10 属于一种蛋白家族，可使一组特定的靶蛋白去泛素化，从而增加其靶亚蛋白组的稳定态蛋白水平。USP10 的靶标之一是 TP53。野生型 TP53 通常可被 USP10 从蛋白酶体降解中拯救。由于大多数 KMT2A 白血病显示野生型 p53 等位基因，因此可以认为 USP10 等位基因的破坏可被归类为致癌事件。
