St. Jude兒童醫(yī)院的研究人員發(fā)明一種嚴重免疫疾病的模型小鼠,。這種小鼠有助于解釋為什么用于治療“泡泡男孩”?。╔SCID,，X連鎖嚴重性綜合免疫缺陷）的為什么導(dǎo)致一些接受治療的兒童發(fā)生了白血病,。XSCID由一種叫做gamma C的基因的突變引發(fā),，這種突變使免疫細胞無法形成B淋巴細胞和T細胞,。
XSCID病因躲在塑料泡泡中防止感染的“泡泡男孩”的故事而聞名。在這種疾病的基因治療中,，gamma C基因的正?？截惐徊迦氲礁杉毎校筮@些干細胞由形成淋巴細胞,。但是,，幾年前在法國進行的這種基因療法的臨床試驗發(fā)些一些接受治療的兒童在治療后患上了白血病，從而使該基因治療試驗被叫停,。通過跟蹤研究接受這種基因治療后發(fā)生白血病的法國患者,，研究人員確定出一些gamma C基因被插入到了致癌基因中。這使干細胞發(fā)生失控的增殖并引發(fā)白血病,。（唯一被廣泛認可的人類基因療法竟會導(dǎo)致癌癥）
這一發(fā)現(xiàn)的一個重要意義在于揭示出其他類型的遺傳血液疾病的基因治療被之前想象的致癌風(fēng)險要小,。這項研究的結(jié)果刊登在8月1日的PNAS上。文章的第一作者是華人研究人員壽言（Yan Shou）博士,，其他文章作者還有馬志軍（Zhijun Ma）和魯泰和（Taihe Lu）,。
研究組利用新的小鼠模型獲得的新發(fā)現(xiàn)為提高XSCID基因療法的安全性、改善療效給出了新的希望,。這項研究部分得到了美國心臟,、肺和血液研究所的資助。
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/ .
