St. Jude儿童医院的研究人员发明一种严重免疫疾病的模型小鼠。这种小鼠有助于解释为什么用于治疗“泡泡男孩”病（XSCID，X连锁严重性综合免疫缺陷）的为什么导致一些接受治疗的儿童发生了白血病。XSCID由一种叫做gamma C的基因的突变引发，这种突变使免疫细胞无法形成B淋巴细胞和T细胞。
XSCID病因躲在塑料泡泡中防止感染的“泡泡男孩”的故事而闻名。在这种疾病的基因治疗中，gamma C基因的正常拷贝被插入到干细胞中，之后这些干细胞由形成淋巴细胞。但是，几年前在法国进行的这种基因疗法的临床试验发些一些接受治疗的儿童在治疗后患上了白血病，从而使该基因治疗试验被叫停。通过跟踪研究接受这种基因治疗后发生白血病的法国患者，研究人员确定出一些gamma C基因被插入到了致癌基因中。这使干细胞发生失控的增殖并引发白血病。（唯一被广泛认可的人类基因疗法竟会导致癌症）
这一发现的一个重要意义在于揭示出其他类型的遗传血液疾病的基因治疗被之前想象的致癌风险要小。这项研究的结果刊登在8月1日的PNAS上。文章的第一作者是华人研究人员寿言（Yan Shou）博士，其他文章作者还有马志军（Zhijun Ma）和鲁泰和（Taihe Lu）。
研究组利用新的小鼠模型获得的新发现为提高XSCID基因疗法的安全性、改善疗效给出了新的希望。这项研究部分得到了美国心脏、肺和血液研究所的资助。
英文原文：
Discovery in 'Bubble Boy' Disease Gene Therapy
St. Jude researchers determine why gene therapy treatment caused leukemia in some severe immune deficiency patients; discovery offers hope for safe treatment
MEMPHIS, Tenn., Aug. 1 /PRNewswire/ -- Scientists at St. Jude Children's Research Hospital have developed a mouse model of a severe disease of the immune system that helps explain why gene therapy used to treat children with this disease at an institution in Europe caused some of them to develop leukemia. The disease, called X-linked severe combined immunodeficiency (XSCID), is caused by a mutation in a gene called gamma C that prevents the immune system from forming B and T lymphocytes.
XSCID was made famous by the story of the so-called "Bubble Boy" who lived inside a plastic "bubble" to shield him from infections. In gene therapy for this disease, normal copies of the gamma C gene are inserted into stem cells that later give rise to these lymphocytes. Following the development of leukemia by the patients in France, researchers determined that some of the gamma C genes had inserted themselves into oncogenes-cancer causing genes. This caused the stem cells to multiply uncontrollably and produce leukemia.
The St. Jude researchers concluded that XSCID itself makes their mouse models-and by extension, children with this disease--particularly susceptible to cancer caused by gene therapy. Specifically, the team found that the population of primitive stem cells that is the target of gene therapy is abnormally large. This increases the chance that gamma C genes that are put into the cells will insert themselves into oncogenes-genes that cause cancer when activated.
One major implication of this finding is that gene therapy for other forms of genetic blood diseases will pose significantly less risk for causing cancer than was previously thought, according to Brian Sorrentino, M.D., director of the St. Jude Experimental Hematology Division and co-director of Transplantation and Gene Therapy. Sorrentino is the senior author of a report on these findings that appears in the August 1 issue of Proceedings of the National Academy of Sciences.
"Our current findings with this new mouse model offer real hope that we can make gene therapy for X-linked SCID safe as well as effective," said Yan Shou, Ph.D., the first author of the paper and the major contributor to this work. Other authors of the paper include Zhijun Ma and Taihe Lu.
This work was supported in part by the National Heart, Lung, and Blood Institute; a Cancer Center Support Grant; the Assisi Foundation of Memphis; and ALSAC.
St. Jude Children's Research Hospital
St. Jude Children's Research Hospital is internationally recognized for its pioneering work in finding cures and saving children with cancer and other catastrophic diseases. Founded by late entertainer Danny Thomas and based in Memphis, Tenn., St. Jude freely shares its discoveries with scientific and medical communities around the world. No family ever pays for treatments not covered by insurance, and families without insurance are never asked to pay. St. Jude is financially supported by ALSAC, its fund-raising organization. For more information, please visit http://www.stjude.org/ .
