生物谷報道：30年來,，國內外科研人員在5號染色體一條“長臂”上,，不斷搜尋可能存在的白血病抑制基因而未能成功,。如今,，在中科院上海生命科學研究院,、上海交大醫(yī)學院共建的健康科學研究所，科學家經(jīng)過三年努力,，已經(jīng)篩選并識別出-連結蛋白基因（alpha-catenin）可能就是那個血癌抑制基因。昨天記者從該所獲悉,，以其為第一單位的相關論文被新年首期國際權威學刊《自然·醫(yī)學》（《Nature Medicine》）刊登,。
人類染色體仿佛一枚枚不對稱的“蝴蝶結”，擁有眾多長臂和短臂,。其中,，5號染色體長臂（5q）會發(fā)生一種雜合性缺失，這是人類造血系統(tǒng)惡性疾病中最常見的染色體結構異常,。尤其在惡性白血病患者中,，其缺失率高達42％。因此,，這一代號為“5q”的染色體長臂,，便成為全球白血病研究人員的一個首選攻關目標。
健康科學所劉廷析研究員帶領發(fā)育與疾病研究組,，與哈佛大學醫(yī)學院達納法伯癌癥研究所等多個實驗室合作,，針對5號染色體長臂的關鍵缺失區(qū)，反復研究其中的28個候選抑制基因,，終于發(fā)現(xiàn)：人體造血干細胞中正常表達的-連結蛋白基因,，在“5q”缺失的白血病腫瘤干細胞中表達顯著下降，甚至丟失,。從而證實,，該基因與白血病關系密切。
這一研究闡明了關于白血病抑制基因失活的分子遺傳學新機制,。即一個-連結蛋白等位基因,，會因基因組片段的缺失而失活，而另一個未缺失的-連結蛋白等位基因,，也會因一種“表觀遺傳學機制”而被抑制,。這種“雙重打擊”顯示，人體正常造血干細胞的遺傳學機制紊亂,，可能在白血病腫瘤干細胞的惡性轉化中起了重要作用,。據(jù)悉，有關動物研究已在斑馬魚身上展開,。
Figure 1. Purification and gene expression analysis of normal HSCs and L-ICs and dual-fluorescence in situ hybridization (D-FISH) analysis of HL-60 cells and purified L-ICs.
(a) Top, normal HSCs enriched for the CD34+CD38-CD90+Lin- fraction. Middle, L-ICs (CD34+CD38-CD123+Lin-) enriched from an individual with del(5q). Bottom, L-ICs (CD34+CD38-CD123+Lin-) from an individual lacking the del(5q). (b–d) D-FISH analysis of HL-60 cells and sorted del(5q) L-ICs from primary leukemia samples. Nuclei of the HL-60 cell line and del(5q) L-ICs from patients V, VII and VIII display two green dots (5p) and one red dot (5q), reflecting loss of one allele of the region of the probe within 164 kb of CTNNA1. (e–g) Non-del(5q) L-ICs from patients XIII and XXII show two green (5p15) and two red (5q31) dots, indicating intact chromosomes 5. (h) Expression profiles of 28 5q CDR genes in HSCs and del(5q)-derived L-ICs. The genes, as well as sequence tag site (STS) markers, are listed in the order of their physical positions (megabase, Mb) along chromosome 5q from centromere (upper) to telomere (bottom), according to the most recent human genome assembly at http://genome.ucsc.edu/. Previously defined 5q31 CDRs are shown schematically on the far left. GAPDH, which resides on chromosome 12, is included as a positive control. MT, verification that intron-spanning RT-PCR primers amplify each of the RNAs, by using a control cDNA prepared from a mixture of 22 human tissues. Single-step RT-PCR was performed with 10-cell aliquots (lanes 1 and 2) and without the RT step (lane –RT, negative control). Asterisks denote the genes expressed in normal HSCs and L-ICs, while the arrowhead indicates the CTNNA1 gene, which was expressed in HSCs, but not in the L-ICs of these three del(5q) individuals.
原文出處：
Nature Medcine January 2007, Volume 13 No 1
Chromosome 5q deletion and epigenetic suppression of the gene encoding -catenin (CTNNA1) in myeloid cell transformation pp78 - 83
Ting Xi Liu, Michael W Becker, Jaroslav Jelinek, Wen-Shu Wu, Min Deng, Natallia Mikhalkevich, Karl Hsu, Clara D Bloomfield, Richard M Stone, Daniel J DeAngelo, Ilene A Galinsky, Jean-Pierre Issa, Michael F Clarke & A Thomas Look
Published online: 10 December 2006 | doi:10.1038/nm1512
Abstract | Full text | PDF (491K) | Supplementary Information
