Gu B-W, Wang Q, Wang J-M, Xue Y-Q, Fang J, Wong K F, Chen B, Shi Z-Z, Shi J-Y, Bai X-T, Wu D-H, Chen Z, Chen S-J
State Key Lab for Medical Genomics, Shanghai Institute of Hematology, Ruijin Hospital Affiliated to Shanghai Second Medical University, Shanghai, People's Republic of China.
Leukemia. 2003 Sep;17(9):1858-64. doi: 10.1038/sj.leu.2403036.
Three adult patients with de novo acute myeloid leukemia of distinct subtypes harboring t(11;12)(p15;q13) have been investigated to characterize the genes involved in that translocation. Through molecular cytogenetics, a chromosome break was detected at the 3' part of nucleoporin 98 (NUP98) gene at 11p15. Using rapid amplification of cDNA end, we identified the partner gene at 12q13, HOXC11. Molecular analysis showed that exon 12 of NUP98 was fused in-frame to exon 2 of HOXC11 in all three cases with t(11;12)(p15;q13). Therefore, this type of fusion may represent the major form of the NUP98-HOXC11 chimera so far reported. Moreover, two out of three cases had a confirmed deletion of the 3' part of NUP98 gene and more telomeric region of 11p harboring a group of tumor-suppressor genes. Interestingly, the NUP98-HOXC11 protein when assayed in a GAL4 reporter system, showed an aberrant trans-regulatory activity as compared to the wild-type HOXC11 in both COS-7 and HL-60 cells. Therefore, NUP98-HOXC11 may contribute to the leukemogenesis by interfering with the cellular mechanism of transcriptional regulation.
对3例患有不同亚型的新发急性髓系白血病且携带t(11;12)(p15;q13)的成年患者进行了研究，以确定参与该易位的基因。通过分子细胞遗传学，在11p15的核孔蛋白98（NUP98）基因的3'部分检测到染色体断裂。利用cDNA末端快速扩增技术，我们在12q13处鉴定出伙伴基因HOXC11。分子分析显示，在所有3例t(11;12)(p15;q13)病例中，NUP98的第12外显子与HOXC11的第2外显子框内融合。因此，这种融合类型可能代表了迄今为止报道的NUP98 - HOXC11嵌合体的主要形式。此外，3例中有2例证实存在NUP98基因3'部分以及11p端粒更远处区域的缺失，该区域含有一组肿瘤抑制基因。有趣的是，在GAL4报告系统中检测时，与野生型HOXC11相比，NUP98 - HOXC11蛋白在COS - 7和HL -
