Martini Alessandra, La Starza Roberta, Janssen Hilde, Bilhou-Nabera Chrystèle, Corveleyn Anniek, Somers Riet, Aventin Ana, Foà Robin, Hagemeijer Anne, Mecucci Christina, Marynen Peter
Center for Human Genetics, University of Leuven, Campus Gasthuisberg O&N06, B-3000 Leuven, Belgium.
Cancer Res. 2002 Oct 1;62(19):5408-12.
Fusions of the TET-proteins (TLS/FUS, EWSR1, and TAF15/RBP56) to different transcription factors are involved in various malignancies including Ewing's sarcoma, primitive neuroectodermal tumors, and acute myeloid leukemia. These are thought to arise through transcriptional deregulation, with the transcription factor defining the tumor phenotype. We show that, as result of a t(12;17)(p13;q11) or its variant t(12;22)(p13;q12), the transcription factor gene CIZ/NMP4 is recurrently involved in acute leukemia through fusion with either EWSR1 or TAF15. The fusions possess transforming properties in NIH3T3 cells but do not affect the expression of CIZ target genes, suggesting a contribution to oncogenesis that is independent of the transactivating properties of the fusion protein. These results also extend the involvement of TET-protein fusions to acute lymphoblastic leukemia and suggest a role for CIZ/NMP4 in lymphoid and myeloid development.
TET 蛋白（TLS/FUS、EWSR1 和 TAF15/RBP56）与不同转录因子的融合参与了多种恶性肿瘤，包括尤因肉瘤、原始神经外胚层肿瘤和急性髓系白血病。这些被认为是通过转录失调产生的，其中转录因子决定肿瘤表型。我们发现，由于 t(12;17)(p13;q11) 或其变体 t(12;22)(p13;q12)，转录因子基因 CIZ/NMP4 通过与 EWSR1 或 TAF15 融合而反复参与急性白血病。这些融合体在 NIH3T3 细胞中具有转化特性，但不影响 CIZ 靶基因的表达，提示其对肿瘤发生的作用独立于融合蛋白的反式激活特性。这些结果还将 TET 蛋白融合的参与范围扩展到急性淋巴细胞白血病，并提示 CIZ/NMP4 在淋巴样和髓样发育中发挥作用。
